The association between vulvodynia and interstitial cystitis/bladder pain syndrome: A systematic review.

BACKGROUND: Vulvodynia (VVD) is a debilitating chronic vulvar pain significantly affecting patients' quality of life. Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic and complex illness characterized by an unpleasant sensation related to the filling of the bladder and it strongly impacts patients' lives. The exact mechanisms of the two syndromes remain unknown, but there is an overlap between suspected pathophysiologies. OBJECTIVE: To present an overview of the current research on the association between VVD and IC/BPS. SEARCH STRATEGY: A systematic search of three electronic databases was conducted. Studies examining the correlation between VVD and IC/BPS with male and female patients aged over 18 years were included. SELECTION CRITERIA: Studies assessing the coexistence of VVD and IC/BPS were included. Reviews, letters to the editor, conference abstracts, book chapters, guidelines, Cochrane reviews, and expert opinions were excluded. DATA COLLECTION AND ANALYSIS: Two reviewers screened the studies for eligibility. Eligible studies were screened for quality. MAIN RESULTS: A total of 13 studies were included in the final review. Among them, 11 presented a positive association between the two syndromes. The studies highlighted that VVD and IC/BPS share common comorbidities and possibly etiopathogenic pathways. CONCLUSION: VVD and IC/BPS are both complex and multifactorial syndromes. This review highlights an association between them, but additional studies on the topic should be conducted for a more precise conclusion.

A Novel Method for the Measurement of the Vaginal Wall Thickness by Transvaginal Ultrasound: A Study of Inter- and Intra-Observer Reliability.

Background and Objectives: A consensus regarding the optimal sonographic technique for measuring vaginal wall thickness (VWT) is still absent in the literature. This study aims to validate a new method for measuring VWT using a biplanar transvaginal ultrasound probe and assess both its intra-operator and inter-operator reproducibility. Material and Methods: This prospective study included patients with genitourinary syndrome of menopause-related symptoms. Women were scanned using a BK Medical Flex Focus 400 with the 65 × 5.5 mm linear longitudinal transducer of an endovaginal biplanar probe (BK Medical probe 8848, BK Ultrasound, Peabody, MA, USA). Vaginal wall thickness (VWT) measurements were acquired from the anterior and posterior vaginal wall at three levels. Results: An inter-observer analysis revealed good consistency between operators at every anatomical site, and the intra-class coefficient ranged from 0.931 to 0.987, indicating high reliability. An intra-observer analysis demonstrated robust consistency in vaginal wall thickness measurements, with an intra-class coefficient exceeding 0.9 for all anatomical sites. Conclusions: The measurement of vaginal wall thickness performed by transvaginal biplanar ultrasound was easy and demonstrated good intra- and inter-operator reliability.

Is weight gain preventable in women with early breast cancer undergoing chemotherapy? A real-world study on dietary pattern, physical activity, and body weight before and after chemotherapy.

PURPOSE: We aimed to investigate the role of a lifestyle intervention and clinical and therapeutic factors for preventing weight gain in early breast cancer (BC) patients from one week before to 12 months after chemotherapy. METHODS: Dietary assessments were conducted by a trained dietician using a food-frequency questionnaire at each clinical assessment. Total energy, macronutrients intakes, and physical activity were estimated and the Mediterranean Diet Score (MDS) for adherence to Mediterranean diet was calculated. At each follow-up visit, patients were provided with dietary advices according to Mediterranean and Italian guidelines by a registered dietician, after evaluation of their food records. The associations of clinical characteristics, dietary pattern, and physical activity with weight gain were evaluated by multiple logistic regression, with weight gain ≥5% from baseline value as a dichotomous dependent variable. RESULTS: 169 early BC patients who met all follow-up visits and provided complete data were included in the analysis. From baseline to last assessment, weight loss (≥5% decrease from baseline value), stable weight, and weight gain were observed in 23.1%, 58%, and 18.9% women, respectively. Overall, a 0.68 kg mean decrease in women's weight (-1.1% from baseline) was observed. The risk of gaining weight increased for having normal weight/underweight at baseline, receiving hormone therapy, MDS worsening, and physical activity decreasing from baseline to last assessment. CONCLUSION: Providing simple suggestions on Mediterranean diet principles was effective for preventing weight gain in normal weight women and favoring weight loss in overweight and obese women.

Prevalence and severity of lower urinary tract symptoms in the third trimester of pregnancy.

INTRODUCTION AND HYPOTHESIS: Pregnancy is a risk factor for urinary disorders, mainly in the third trimester. Lower urinary tract symptoms (LUTS) are often underreported by health care professionals and significantly impact the quality of life of pregnant women. Our objective is to analyse lower urinary tract function during the third trimester of pregnancy and assess the impact of traditional risk factors for pelvic floor dysfunctions on bladder health in pregnant women. METHODS: This is a secondary analysis of a multicentre cross-sectional study. Third-trimester pregnant women aged 18 years or older anonymously filled in the "Italian Pelvic Floor Questionnaire for pregnant and postpartum women" questionnaire, validated for pelvic floor disorders in pregnancy and postpartum. RESULTS: A total of 927 pregnant patients completed the questionnaire. Among them, 97.3% complained of at least one urinary disorder. Frequency was the symptom reported most often (77.3%), whereas nocturnal enuresis was the least reported (17%). Despite the high prevalence of LUTS in our sample, only 13.4% reported that they negatively impact their quality of life. Overweight and obesity, advanced maternal age, smoking, family history of pelvic floor disorders and poor pelvic floor contraction capacity were confirmed to be risk factors for the onset of LUTS, even in our population. CONCLUSIONS: Urinary symptoms are extremely common in the third trimester and significantly affect the quality of life of pregnant women. Since overweight, obesity, smoking and reduced pelvic floor contractility emerged as modifiable risk factors for the development of these symptoms, prevention and adequate counselling are cornerstones of pregnancy care.

Outcomes of High-Grade Cervical Dysplasia with Positive Margins and HPV Persistence after Cervical Conization.

The objective of this work is to assess the 5-year outcomes of patients undergoing conization for high-grade cervical lesions that simultaneously present as risk factors in the persistence of HPV infection and the positivity of surgical resection margins. This is a retrospective study evaluating patients undergoing conization for high-grade cervical lesions. All patients included had both positive surgical margins and experienced HPV persistence at 6 months. Associations were evaluated with Cox proportional hazard regression and summarized using hazard ratio (HR). The charts of 2966 patients undergoing conization were reviewed. Among the whole population, 163 (5.5%) patients met the inclusion criteria, being at high risk due to the presence of positive surgical margins and experiencing HPV persistence. Of 163 patients included, 17 (10.4%) patients developed a CIN2+ recurrence during the 5-year follow-up. Via univariate analyses, diagnosis of CIN3 instead of CIN2 (HR: 4.88 (95%CI: 1.10, 12.41); p = 0.035) and positive endocervical instead of ectocervical margins (HR: 6.44 (95%CI: 2.80, 9.65); p < 0.001) were associated with increased risk of persistence/recurrence. Via multivariate analyses, only positive endocervical instead of ectocervical margins (HR: 4.56 (95%CI: 1.23, 7.95); p = 0.021) were associated with worse outcomes. In this high-risk group, positive endocervical margins is the main risk factor predicting 5-year recurrence.

Taste Alterations Do Not Affect Change in Food Habits and Body Weight in Breast Cancer Patients.

BACKGROUND/AIM: Chemotherapy-induced taste alterations (TAs) affect approximately 53-84% of breast cancer patients with significant consequences on flavor perception, possibly leading to food aversion and changes in daily dietary habits. The aim of this study was to investigate the relationship between TAs and changes in food habits and body weight among early breast cancer (EBC) patients undergoing adjuvant chemotherapy. PATIENTS AND METHODS: TAs were prospectively evaluated in 182 EBC patients from April 2014 to June 2018. TAs, dietary habits, and body weight were collected by a trained dietician. TAs were classified into different subtypes according to the following basic taste perception: metallic, sweet, bitter, salty, sour, and umami taste. RESULTS: During adjuvant chemotherapy, a significant reduction in the consumption of bread, breadsticks, red meat, fat salami, snacks, added sugar, milk, and alcoholic beverages was observed, regardless of TAs onset. No correlation between these dietary changes and different TAs subtypes was found. Body weight remained stable in most EBC patients (71.4%) and was not influenced by TAs onset and by different TAs subtypes. CONCLUSION: EBC patients change their dietary habits during adjuvant chemotherapy, mostly following the World Cancer Research Fund recommendations, irrespective of TAs onset and without affecting body weight.

Taste alterations during neo/adjuvant chemotherapy and subsequent follow-up in breast cancer patients: a prospective single-center clinical study.

PURPOSE: Dysgeusia and taste alterations (TAs) are side effects of cytotoxic chemotherapy and affect patients' quality of life; however, the prevalence, types, and duration of TAs and their potential relationship with other clinical disturbances are not well-described. Our primary aim was to prospectively evaluate the characteristics of TAs in early breast cancer (EBC) patients during (neo)adjuvant chemotherapy and up to 1 year after its completion. METHODS: From April 2014 to June 2018, 182 EBC patients entered the study and received (neo)adjuvant chemotherapy, mostly with taxane and anthracycline-containing regimens (65% of cases). A dietitian performed TAs assessment through the Common Terminology Criteria for Adverse Event v4.0 (CTCAE) and the Chemotherapy-induced Taste Alteration Scale (CiTAS) questionnaire during chemotherapy and follow-up according to defined time points: at baseline (T0, before starting chemotherapy); at the first follow-up visit, (T1, 2 months after starting chemotherapy); at the final follow-up visit (T2, 1 week after completing chemotherapy); after that, every 3 months up to 12 months. RESULTS: Dysgeusia was reported by 69.8% of patients at T1 and declined subsequently; salty flavor distortion was the most frequently reported TA (51.6% of cases). CiTAS was significantly different between T0 and T2 (p < 0.001). Dysgeusia occurred more frequently in patients reporting nausea, mucositis, diarrhea, and appetite modification. CONCLUSIONS: TAs are common but transient during chemotherapy and occurred frequently with other distressing gastrointestinal side effects. The assessment of these side effects is crucial in managing EBC patients during (neo)adjuvant chemotherapy.

Development of a Nomogram Predicting the Risk of Persistence/Recurrence of Cervical Dysplasia.

Background: Cervical dysplasia persistence/recurrence has a great impact on women's health and quality of life. In this study, we investigated whether a prognostic nomogram may improve risk assessment after primary conization. Methods: This is a retrospective multi-institutional study based on charts of consecutive patients undergoing conization between 1 January 2010 and 31 December 2014. A nomogram assessing the importance of different variables was built. A cohort of patients treated between 1 January 2015 and 30 June 2016 was used to validate the nomogram. Results: A total of 2966 patients undergoing primary conization were analyzed. The median (range) patient age was 40 (18-89) years. At 5-year of follow-up, 6% of patients (175/2966) had developed a persistent/recurrent cervical dysplasia. Median (range) recurrence-free survival was 18 (5-52) months. Diagnosis of CIN3, presence of HR-HPV types, positive endocervical margins, HPV persistence, and the omission of HPV vaccination after conization increased significantly and independently of the risk of developing cervical dysplasia persistence/recurrence. A nomogram weighting the impact of all variables was built with a C-Index of 0.809. A dataset of 549 patients was used to validate the nomogram, with a C-index of 0.809. Conclusions: The present nomogram represents a useful tool for counseling women about their risk of persistence/recurrence after primary conization. HPV vaccination after conization is associated with a reduced risk of CIN2+.

Stem Cells in Clinical Trials for Pelvic Floor Disorders: a Systematic Literature Review.

Pelvic floor disorders (PFDs) include a series of conditions that can be poorly tolerated, negatively affecting the quality of life. Current treatment options show unsatisfactory results and new ones are therefore needed. Stem cell (SC) therapy might be an alternative treatment strategy. This systematic review aims to define the state of art of SC therapy for PFDs in clinical trials, by systematically reviewing the available evidence. A systematic search strategy was conducted up to November 7, 2020, in PubMed, Scopus, Cochrane Library, and ISI Web of Science. Preclinical studies on animal models were not considered. Studies were included when the patients were affected by any PFDs and cells were isolated, cultured, and characterized as SC. The study protocol was registered in PROSPERO (CRD42020216551). A total of 11 prospective clinical studies were included in the final assessment, specifically 7 single-arm studies dealing with SC therapy for stress urinary incontinence and 4 with anal incontinence. Among the latter, there were two prospective, single-arm studies and two randomized controlled trials. No papers concerning the use of SC for prolapse repair were retrieved. Due to the great heterogeneity, data pooling was not possible. Stem cell injection resulted in a safe procedure, with few mild adverse side effects, mostly related to harvesting sites. However, a clear beneficial impact of SC treatment for the treatment of pelvic floor disorders could not be demonstrated. Further larger targeted studies with control arms are needed before any conclusions can be made.

Changes in eating habits and food preferences in breast cancer patients undergoing adjuvant chemotherapy.

Change in eating habits in early breast cancer (EBC) patients during chemotherapy has been poorly studied in the literature. The primary aim of this study was to prospectively evaluate food preferences and weight change in EBC patients before and after adjuvant chemotherapy. From April 2014 to June 2018, 205 EBC patients underwent a dietary assessment according to the following timeline: baseline evaluation (one week before starting chemotherapy, T0); first follow-up (approximately 2-3 months after starting chemotherapy, T1); final follow-up (one week after chemotherapy end, T2). A statistically significant reduction of the following foods was reported after the start of chemotherapy: pasta or rice, bread, breadsticks/crackers, red meat, fat and lean salami, fresh and aged cheese, milk, yogurt, added sugar, soft drinks, alcoholic beverages (wine, beer, and schnapps), and condiments (oil and butter). Conversely, fruit consumption consistently increased. As a result of these changes, a Healthy Eating Index (HEI) specifically developed for this study and suggestive of a balanced diet, significantly increased. Body weight did not increase, despite reduction in physical activity. This prospective study shows that EBC patients tend to adopt "healthier dietary patterns" during adjuvant chemotherapy, leading to a non-change in weight, despite reduction in physical activity.

High-risk HPV-positive and -negative high-grade cervical dysplasia: Analysis of 5-year outcomes.

OBJECTIVE: To evaluate the outcomes of high-risk (HR) HPV-positive and -negative women affected by high-grade cervical dysplasia. METHODS: This is a retrospective multi-institutional study. Medical records of consecutive patients with high-grade cervical dysplasia undergoing conization between 2010 and 2014 were retrieved. All patients included had at least 5 years of follow-up. A propensity-score matching was adopted in order to reduce the presence of confounding factors between groups. Kaplan-Meir and Cox hazard models were used to estimate 5-year outcomes. RESULTS: Overall, data of 2966 women, affected by high-grade cervical dysplasia were reviewed. The study population included 1478 (85%) and 260 (15%) women affected by HR-HPV-positive and HR-HPV-negative high-grade cervical dysplasia. The prevalence of CIN2 and CIN3 among the HR-HPV-positive and -negative cohort was similar (p = 0.315). Patients with HR-HPV-positive high-grade cervical dysplasia were at higher risk of 5-year recurrence (after primary conization) that HR-HPV-negative patients (p < 0.001, log-rank test). Via multivariate analysis, HR-HPV-negative women were at low risk of recurrence (HR: 1.69 (95%CI: 1.05, 4.80); p = 0.018, Cox Hazard model). A propensity-score matched comparison was carried out in order to reduce biases that are related to the retrospective study design. In comparison to HR-HPV-negative patients, thosewith HR-HPV-positive CIN3 was associate with a 8-fold increase in the risk of recurrence (p < 0.001, log-rank test). CONCLUSIONS: HR-HPV-negative high-grade cervical dysplasia is not uncommon, accounting for 15% of our study population. Those patients experience more favorable outcomes than patients with documented HR-HPV infection(s). Further prospective studies are needed to corroborate our data.

Telephone interview in urogynecology in the era of COVID-19 pandemic

Objective: During the Coronavirus disease-2019 (COVID-19) pandemic deferable access, including non-urgent outpatient visits, have been suspended. In our practice non-urgent routine visits for pelvic floor symptom assessment were discontinued and rescheduled, and telephone interview was performed. The aim was to evaluate patients' satisfaction for this alternative approach. Material and Methods: Telephone interviews were conducted using a validated questionnaire to investigate pelvic floor symptoms. Patients were also asked if they had other symptoms or disorders, to identify patients who may need urgent hospital evaluation. At the end of the phone call, patients were asked to score their satisfaction with the telephone interview by grading their response to three questions from 0 (minimum) to 10 (maximum). The questions were: 1) "Was the telephone interview useful to check your state of health?"; 2) "Was the telephone interview an adequate healthcare tool in consideration of COVID-19 outbreak?"; 3) "Could the telephone interview replace the conventional visit?". Results: Fifty-three patients were evaluated. All patients showed great satisfaction with telephone interview (Q1 median: 10, IQ range: 10-10) and were similarly positive in response to the second question (Q2 median: 10, IQ range: 10-10). Although fewer patients felt that telephone interview could replace conventional clinic visits most remained positive (Q3 median: 7; IQ range: 6-8). Conclusion: This simple experience showed that phone interviews with validated questionnaires are appreciated and effective to safely perform interview of selected urogynecologic patients.

Patterns of failure after adjuvant "sandwich" chemo-radio-chemotherapy in locally advanced (stage III-IVA) endometrial cancer.

PURPOSE: To investigate oncological outcomes and patterns of recurrence of patients undergoing adjuvant "sandwich" chemo-radio-chemotherapy for locally advanced endometrial cancer. METHODS: This is a multi-institutional retrospective study evaluating chart of consecutive patients undergoing chemo-radio-chemotherapy for FIGO stage III-IVA endometrial caner. RESULTS: The study population included 45 patients who had adjuvant sandwich regimen. Median age of the study population was 66 years. The majority of patients were diagnosed with endometrioid histology and with stage III disease. After a median follow-up of 35 months, 15 patients developed recurrent disease. Three-year disease-free and overall survivals was 45% and 81%, respectively. Three-years site-specific disease-free survival was 85%, 92% and 48% for local, loco-regional, and distant recurrence, respectively. All patients included in the study had nodal dissection. Nodal assessment included: sentinel node mapping, sentinel node mapping plus backup lymphadenectomy and lymphadenectomy in 15, 6 and 24 patients, respectively. The latter group included four patients detected by suspected enlarged nodes, intraoperatively. Even after the exclusion of patients with enlarged nodes, the type of nodal assessment did not impact on survival outcomes (p > 0.2). Positive peritoneal cytology was the only factor associated with an increased risk of developing (any site) recurrence and distant-specific recurrence, independently. No factor predicted for overall survival. CONCLUSION: Adjuvant "sandwich" chemo-radio-chemotherapy for locally advanced endometrial cancer guarantee promising local and loco-regional controls, but distant failure rate is high, thus suggesting the need for applying other systemic treatment strategies for these patients.

Recurrence rate after loop electrosurgical excision procedure (LEEP) and laser Conization: A 5-year follow-up study.

OBJECTIVE: Conization aims to remove pre-neoplastic lesions of the uterine cervix. Several techniques for conization have been compared, but evidence regarding the most effective therapeutic option is scant. Here, we aimed to compare the recurrence rate following laser conization and loop electrosurgical excision procedure (LEEP) in patients with high-grade cervical dysplasia (HSIL/CIN2+). METHODS: This is a retrospective multi-institutional study. Medical records of consecutive patients with HSIL/CIN2+ undergoing conization between 2010 and 2014 were retrieved. A propensity-score matching (PSM) was applied in order to reduce allocation bias. The risk of developing recurrence was estimated using Kaplan-Meir and Cox hazard models. RESULTS: Overall, 2966 patients had conization over the study period, including 567 (20%) and 2399 (80%) patients having laser conization and LEEP, respectively. Looking at predictors of recurrence, diagnosis of CIN3 (HR:3.80 (95%CI:2.01,7.21); p < 0.001) and HPV persistence (HR:1.81 (95%CI:1.11,2.96); p < 0.001) correlated with an increased risk of recurrence. After applying a PSM we selected 500 patients undergoing laser conization and 1000 undergoing LEEP. Patients undergoing LEEP were at higher risk of having positive surgical margins in comparison to patients undergoing laser conization (11.2% vs. 4.2%). The risk of having persistence of HPV was similar between the two groups (15.0% vs. 11.6%;p = 0.256). Five-year recurrence rate was 8.1% and 4% after LEEP and laser conization, respectively (p = 0.023). HPV persistence was the only factor associated with [5-]year recurrence after both laser conization (p = 0.003) and LEEP (p = 0.001). CONCLUSIONS: HPV persistence is the only factor associated with an increased risk of recurrence after either laser conization or LEEP. Owing to the lack of data regarding obstetrical outcomes, we are not able to assess the best therapeutic option for women with cervical dysplasia.

Immunotherapy for platinum-resistant ovarian cancer.

Ovarian cancer is characterized by a high mortality on incidence ratio. Although the majority of patients achieve complete response after primary treatment, approximately 65-80% of patients recur with the first 5 years. Platinum-free interval is one of the main prognostic factors. Patients recurring with 6 months within the end of platinum-based chemotherapy are characterized by poor prognosis. To date no effective treatment modality are identified for those patients. The mainstay of treatment for platinum-resistant ovarian cancer is single agent chemotherapy. Other treatment modalities have tested in this setting with discouraging results. Growing evidence suggested that immunotherapy would improve outcomes of patients with various types of solid tumors including melanoma, non-small cell lung cancer as well as uterine malignancies. Here, we reviewed current evidence on the adoption of immunotherapy in platinum-resistant ovarian cancer. To date no mature evidence supports the routine adoption of immunotherapy in ovarian cancer patients. Further strategies have to be explored.

Cancer patients affected by COVID-19: Experience from Milan, Lombardy.

OBJECTIVE: SARS-CoV-2 pandemic is continuing to spread. There are growing concerns on the impact of COVID-19 in cancer patients. Several papers reporting recommendations and guidelines are published. But few data on cancer patients affected by COVID-19 are available. METHODS: This is a retrospective study including all consecutive patients affected by gynecological cancer who developed COVID-19. All patients were treated in an academic setting (in Milan, Lombardy, Italy) between February and March 2020. RESULTS: Overall, 355 patients had active treatment during the study period due to newly diagnosed or recurrent gynecological disease. Among those, 19 (5.3%) patients affected developed COVID-19. All patients were asymptomatic at the time of COVID-19 detection. Six patients were diagnosed before starting planned treatments; while the remaining 13 were diagnosed for COVID-19 after their started their treatments. Considering the first group of six patients, one patient died due to COVID-19 3 days after the diagnosis; while the other patients recovered from COVID-19 after a median of three weeks. The latter group of 13 patients (treatments started) included five patients who underwent surgery and eight patients who underwent chemotherapy. Focusing on five patients who were diagnosed after surgery, we observed that two patients died during postoperative course, while in other two cases prolonged hospitalization was needed. One patient had no issues. Chemotherapy was delayed for the remaining patents without sequelae. CONCLUSIONS: Our report highlights that COVID-19 impacts the quality of treatments for cancer patients. Mortality rate is high, especially after surgery. More important, patients under active treatment for cancer are at high risk of developing severe evolution of COVID-19. Prioritizing patients journey during COVID-19 is of paramount importance.

Management of patients with ovarian cancer in the COVID-19 era.

At the beginning of 2020, coronavirus disease 2019 (COVID-19) spreads worldwide. Patients with ovarian cancer should be considered at high-risk of developing severe morbidity related to COVID-19. Most of them are diagnosed in advanced stages of disease, and they are fragile. Here, we evaluated the major impact of COVID-19 on patients with ovarian cancer, discussing the effect of the outbreak on medical and surgical treatment.

The reaction of singlet oxygen with enecarbamates: a mechanistic playground for investigating chemoselectivity, stereoselectivity, and vibratioselectivity of photooxidations.

Photochirogenesis, the control of chirality in photoreactions, is one of the most challenging problems in stereocontrolled photochemistry, in which the stereodifferentiation has to be imprinted within the short lifetime of the electronically excited state. Singlet oxygen (1O2), an electronically excited molecule that is known to be sensitive to vibrational deactivation, has been selected as a model case for testing stereoselective control by vibrational deactivation. The stereoselectivity in the reaction of 1O2 with E/Z enecarbamates 1, equipped with the oxazolidinone chiral auxiliary, has been examined for the mode selectivity ([2 + 2]-cycloaddition versus ene-reaction) and the stereoselectivity in the oxidative cleavage of the alkenyl functionality to the methyldesoxybenzoin (MDB) product. Through the appropriate choice of substituents in the enecarbamate, the mode selectivity (ene versus [2 + 2]), which depends on the alkene geometry (E or Z), the steric bulk of the oxazolidinone substituent at the C-4 position, and the C-3' configuration on the side chain, may be manipulated. Phenethyl substitution gives exclusively the [2 + 2]-cycloaddition product, irrespective of the alkene geometry. The stereoselection in the resulting methyldesoxybenzoin (MDB) product is examined in a variety of solvents as a function of temperature by using chiral GC analysis. The extent (% ee) as well as the sense (R versus S) of the stereoselectivity in the MDB formation for the E isomer depends significantly on solvent and temperature, whereas the corresponding Z isomers are not affected by such variations. The complex temperature and solvent effects are scrutinized in terms of the differential activation parameters (DeltaDeltaS++, DeltaDeltaH++) for the photooxygenation of E/Z-enecarbamates in various solvents at different temperatures. The enthalpy-entropy compensations provide a mechanistic understanding of the temperature dependence of the ee values for the MDB product and the difference in the behavior between the Z and E enecarbamates. The E enecarbamates show a relatively high contribution from the entropy term and an appreciable contribution from the enthalpy term; both terms possess the same sign. In contrast, the corresponding relative insensitivity of Z enecarbamates to temperature and solvent variation is convincingly explained by the near-zero DeltaDelta S++ and DeltaDelta H++. Such effects, associated with temperature- and solvent-dependent conformational factors, are most likely dictated by the stereogenic center at the C-3' phenethyl substituent. The high stereocontrol during the photooxygenation of the chiral enecarbamates is shown to be independent of the steric demand of the oxazolidinone substituent at the C-4 position. In view of the reduced stereocontrol on deuteration of the oxazolidinone substituent at the C-4 position, we propose that the unusual stereoselective vibrational quenching of the attacking singlet oxygen (excited-state reactivity), a novel mechanistic concept, works in concert with the usual steric impositions (ground-state reactivity) exercised by the substituents to afford the high stereoselectivity observed in the dioxetane product during the [2 + 2] cycloaddition. Such synergistic interplay is held responsible for the highly stereoselective photooxidative cleavage of the chiral enecarbamates. The efficacy of stereocontrol in this photooxidation is demonstrated by kinetically resolving the epimers of the enecarbamate cleavage product (MDB) in essentially perfect stereoselectivity, a new methodology that we coin "photo-Pasteur-type kinetic resolution".

Enecarbamates as selective substrates in oxidations: chiral-auxiliary-controlled mode selectivity and diastereoselectivity in the [2+2] cycloaddition and ene reaction of singlet oxygen and in the epoxidation by DMD and mCPBA.

The stereochemical course of the oxidation of chiral oxazolidinone-substituted enecarbamates has been studied for singlet oxygen ((1)O(2)), dimethyldioxirane (DMD), and m-chloroperbenzoic acid (mCPBA) by examining of the special structural and stereoelectronic features of the enecarbamates. Valuable mechanistic insight into these selective oxidations is gained. Whereas the R(1) substituent on the chiral auxiliary is responsible for the steric shielding of the double bond and determines the sense of the pi-facial diastereoselectivity, structural characteristic such as the Z/E configuration and the nature of the R(2) group on the double bond are responsible for the extent of the diastereoselectivity. Stereoelectronic steering by the vinylic nitrogen functionality controls the mode selectivity (ene reaction vs [2+2] cycloaddition) in the case of (1)O(2).

Stereochemical features of the physical and chemical interactions of singlet oxygen with enecarbamates.

Oxazolidinone-substituted enecarbamates represent a mechanistically rich system for the study of stereoelectronic, steric, and conformational effects on stereoselectivity and mode selectivity in (1)O(2) [2 + 2] and ene reactions. Photooxygenation of these enecarbamates with (1)O(2) leads to diastereomerically pure dioxetanes that decompose to yield an oxazolidinone carbaldehyde and one of the two enantiomers of methyldesoxybenzoin in enantiomeric excess. Stereoselectivity originates at the allylic stereocenter, a result supported by quenching studies, computational analysis, and deuterium solvent isotope effects. [reaction: see text]