Intermolecular Enantioselective Amination Reactions Mediated by Visible Light and a Chiral Iron Porphyrin Complex.

In the presence of 1 mol% of a chiral iron porphyrin catalyst, various 3-arylmethyl-substituted 2-quinolones and 2-pyridones underwent an enantioselective amination reaction (20 examples; 93-99% ee). The substrates were used as the limiting reagents, and fluorinated aryl azides (1.5 equiv.) served as nitrene precursors. The reaction is triggered by visible light which allows a facile dediazotation at ambient temperature. The selectivity of the reaction is governed by a two-point hydrogen bond interaction between the ligand of the iron catalyst and the substrate. Hydrogen bonding directs the amination to a specific hydrogen atom within the substrate that is displaced by the nitrogen substituent either in a concerted fashion or by a rebound mechanism.

Experts' recommendations in laser use for the treatment of bladder cancer: a comprehensive guide by the European Section of Uro-Technology (ESUT) and Training and Research in Urological Surgery and Technology (TRUST)-Group.

PURPOSE: To identify laser settings and limits applied by experts during laser vaporization (vapBT) and laser en-bloc resection of bladder tumors (ERBT) and to identify preventive measures to reduce complications. METHODS: After a focused literature search to identify relevant questions, we conducted a survey (57 questions) which was sent to laser experts. The expert selection was based on clinical experience and scientific contribution. Participants were asked for used laser types, typical laser settings during specific scenarios, and preventive measures applied during surgery. Settings for a maximum of 2 different lasers for each scenario were possible. Responses and settings were compared among the reported laser types. RESULTS: Twenty-three of 29 (79.3%) invited experts completed the survey. Thulium fiber laser (TFL) is the most common laser (57%), followed by Holmium:Yttrium-Aluminium-Garnet (Ho:YAG) (48%), continuous wave (cw) Thulium:Yttrium-Aluminium-Garnet (Tm:YAG) (26%), and pulsed Tm:YAG (13%). Experts prefer ERBT (91.3%) to vapBT (8.7%); however, relevant limitations such as tumor size, number, and anatomical tumor location exist. Laser settings were generally comparable; however, we could find significant differences between the laser sources for lateral wall ERBT (p = 0.028) and standard ERBT (p = 0.033), with cwTm:YAG and pulsed Tm:YAG being operated in higher power modes when compared to TFL and Ho:YAG. Experts prefer long pulse modes for Ho:YAG and short pulse modes for TFL lasers. CONCLUSION: TFL seems to have replaced Ho:YAG and Tm:YAG. Most laser settings do not differ significantly among laser sources. For experts, continuous flow irrigation is the most commonly applied measure to reduce complications.

Enantioselective Intramolecular ortho Photocycloaddition Reactions of 2-Acetonaphthones.

2-Acetonaphthones, which bear an alkenyl group tethered to its C1 carbon atom via an oxygen atom, were found to undergo an enantioselective intramolecular ortho photocycloaddition reaction. A chiral oxazaborolidine Lewis acid leads to a bathochromic absorption shift of the substrate and enables an efficient enantioface differentiation. Visible light irradiation (λ=450 nm) triggers the reaction which is tolerant of various groups at almost any position except carbon atom C8 (16 examples, 53-99 % yield, 80-97 % ee). Consecutive reactions were explored including a sensitized rearrangement to tetrahydrobiphenylenes, which occurred with full retention of configuration. Evidence was collected that the catalytic photocycloaddition occurs via triplet intermediates, and the binding mode of the acetonaphthone to the chiral Lewis acid was elucidated by DFT calculations.

Enantioselective, Intermolecular [π2+σ2] Photocycloaddition Reactions of 2(1H)-Quinolones and Bicyclo[1.1.0]butanes.

1-Substituted bicyclo[1.1.0]butanes add enantioselectively to 2(1H)-quinolones upon irradiation (λ = 366 nm) in the presence of a chiral complexing agent. A two-point hydrogen bond between the quinolone and the template is responsible for stereocontrol in the photocycloaddition reaction. The reaction leads to the formation of products with a chiral bicyclo[2.1.1]hexane skeleton in high enantiomeric excess (91-99% ee). The chiral template can be almost quantitatively (97%) recovered and used in another reaction. A triplet reaction pathway is likely, and sensitization is a suitable tool if the reaction is to be performed with visible light (λ = 420 nm).

Creating a Defined Chirality in Amino Acids and Cyclic Dipeptides by Photochemical Deracemization.

2,5-Diketopiperazines are cyclic dipeptides displaying a wide range of applications. Their enantioselective preparation has now been found possible from the respective racemates by a photochemical deracemization (53 examples, 74 % to quantitative yield, 71-99 % ee). A chiral benzophenone catalyst in concert with irradiation at λ=366 nm enables to establish the configuration at the stereogenic carbon atom C6 at will. If other stereogenic centers are present in the diketopiperazines they remain unaffected and a stereochemical editing is possible at a single position. Consecutive reactions, including the conversion into N-aryl or N-alkyl amino acids or the reduction to piperazines, occur without compromising the newly created stereogenic center. Transient absorption spectroscopy revealed that the benzophenone catalyst processes one enantiomer of the 2,5-diketopiperazines preferentially and enables a reversible hydrogen atom transfer that is responsible for the deracemization process. The remarkably long lifetime of the protonated ketyl radical implies a yet unprecedented mode of action.

Experts' recommendations in laser use for the endoscopic treatment of prostate hypertrophy: a comprehensive guide by the European Section of Uro-Technology (ESUT) and Training-Research in Urological Surgery and Technology (T.R.U.S.T.)-Group.

PURPOSE: To identify expert laser settings for BPH treatment and evaluate the application of preventive measures to reduce complications. METHODS: A survey was conducted after narrative literature research to identify relevant questions regarding laser use for BPH treatment (59 questions). Experts were asked for laser settings during specific clinical scenarios. Settings were compared for the reported laser types, and common settings and preventive measures were identified. RESULTS: Twenty-two experts completed the survey with a mean filling time of 12.9 min. Ho:YAG, Thulium fiber laser (TFL), continuous wave (cw) Tm:YAG, pulsed Tm:YAG and Greenlight™ lasers are used by 73% (16/22), 50% (11/22), 23% (5/22), 13.6% (3/22) and 9.1% (2/22) of experts, respectively. All experts use anatomical enucleation of the prostate (EEP), preferentially in one- or two-lobe technique. Laser settings differ significantly between laser types, with median laser power for apical/main gland EEP of 75/94 W, 60/60 W, 100/100 W, 100/100 W, and 80/80 W for Ho:YAG, TFL, cwTm:YAG, pulsed Tm:YAG and Greenlight™ lasers, respectively (p = 0.02 and p = 0.005). However, power settings within the same laser source are similar. Pulse shapes for main gland EEP significantly differ between lasers with long and pulse shape modified (e.g., Moses, Virtual Basket) modes preferred for Ho:YAG and short pulse modes for TFL (p = 0.031). CONCLUSION: Ho:YAG lasers no longer seem to be the mainstay of EEP. TFL lasers are generally used in pulsed mode though clinical applicability for quasi-continuous settings has recently been demonstrated. One and two-lobe techniques are beneficial regarding operative time and are used by most experts.

Photochemical Isomerization of Cyclohept-1-ene-1-carbaldehyde: Strain-Release Cycloadditions and Ene Reactions.

Cyclohept-1-ene-1-carbaldehyde undergoes photoinduced E → Z isomerization at λ = 350 nm. The ring strain facilitates Diels-Alder cycloaddiions with 1,3-dienes, [3 + 2] cycloadditions with 1,3-dipoles, and ene reactions with olefins. Products are trans-fused at the cycloheptane core and were obtained in yields of up to 82%. Single crystal X-ray analyses corroborated the constitution and relative configuration of key products. With BF3 as a Lewis acid and 2,3-dimethylbuta-1,3-diene, cyclohept-1-ene-1-carbaldehyde reacted in the dark and rearranged stereoselectively to a tricyclic ketone (87%).

Total Synthesis of (-)-5-Deoxyenterocin and Attempted Late-Stage Functionalization Reactions.

The first total synthesis of (-)-5-deoxyenterocin has been accomplished starting from pentane-1,3,5-triol (16 steps in the longest linear sequence, 0.2 % overall yield). (-)-Menthone served as the source of chirality to distinguish the enantiotopic hydroxymethyl groups of the substrate. Key steps of the synthesis include two aldol reactions to either end of the C5 -skeleton, a diastereoselective hydroxylation reaction and a biomimetic twofold intramolecular aldol reaction as the final step. Although this step suffered from geometrical constraints and was low yielding (10 %), enough synthetic material could be secured to substantiate the relative and absolute configuration of the natural product. Additional experiments were directed toward a C-H functionalization at carbon atom C5. Despite the fact that several protocols could be successfully applied to (3aR)-(+)-sclareolide as model substrate, (-)-5-deoxyenterocin withstood any selective functionalization.

Catalytic Photochemical Deracemization via Short-Lived Intermediates.

Upon irradiation in the presence of a suitable chiral catalyst, racemic compound mixtures can be converted into enantiomerically pure compounds with the same constitution. The process is called photochemical deracemization and involves the formation of short-lived intermediates. By opening different reaction channels for the forward reaction to the intermediate and for the re-constitution of the chiral molecule, the entropically disfavored process becomes feasible. Since the discovery of the first photochemical deracemization in 2018, the field has been growing rapidly. This review comprehensively covers the research performed in the area and discusses current developments. It is subdivided according to the mode of action and the respective substrate classes. The focus of this review is on the scope of the individual reactions and on a discussion of the mechanistic details underlying the presented reaction.

Total Synthesis of (+)-Prezizaan-15-ol, (+)-Jinkohol II, and (+)-Jinkoholic Acid.

A recently developed photochemical cascade reaction provides access to diastereomeric pentacyclic products, which display the carbon skeleton of prezizane natural products. The minor diastereoisomer with a 2ß-Me configuration was converted in 12 reaction steps into (+)-prezizaan-15-ol. The major diastereoisomer with a 2α-Me configuration gave in an analogous route (+)-jinkohol II, which was oxidized at C13 to (+)-jinkoholic acid. A previous ambiguity regarding the configuration of the natural products could be clarified by total synthesis.

Diastereoselective, Lewis acid-mediated Diels-Alder reactions of allenoic acid derivatives and 1,3-cyclopentadienes.

Allenes with different substituents at their terminal carbon atom display axial chirality and can be obtained in enantiopure form by a photochemical deracemization protocol. It has now been studied under which conditions allenoic acid derivatives undergo a Diels-Alder reaction with 1,3-cyclopentadienes and which products result. Cyclic derivatives (lactams, lactones) underwent an exo-selective reaction catalyzed by the Lewis acid Eu(fod)3, while acyclic derivatives yielded with high preference the endo-products (EtAlCl2 as the preferred Lewis acid). The exocyclic double bond forms with exquisite diastereoselectivity and the chirality transfer is close to perfect. The method was applied to the synthesis of the sesquiterpenes ß-santalol (1) and 10(E)-ß-santalic acid (13).

Functional and oncological outcomes after radical prostatectomy in patients with history of surgery for lower urinary tract symptoms related to benign prostatic enlargement: A systematic review with meta-analysis.

BACKGROUND: Outcomes of radical prostatectomy (RP) in men with history of lower urinary tract symptoms related to benign prostatic enlargement (LUTS/BPE) surgery represents a controversial issue. We performed an updated systematic review and meta- analysis evaluating oncological and functional outcomes of RP in this subset of patients. METHODS: Eligible studies were identified from MEDLINE, Web of Science and the Scopus databases. The following outcomes were evaluated: incidence of positive surgical margins (PSM), incidence of biochemical recurrence (BCR), 3-mo and 1-year urinary continence (UC) rates, incidence of nerve-sparing (NS) procedures, 1-year erectile function (EF) recovery rates. We estimated pooled Odds ratios (OR) and 95% confidence intervals (CI) using random effects models. Sub-analyses were performed according to the type of RP and LUTS/BPE surgery. RESULTS: Twenty-five retrospective studies including 11,101 patients undergoing RP were included in the analysis (2113 with history of LUTS/BPE surgery, and 8898 controls). PSM rate was significantly higher in patients with history of LUTS/BPE surgery (OR 1.39, 95% CI 1.18-1.63, p < 0.001). No statistically significant difference in terms of BCR emerged between patients with or without history of LUTS/BPE surgery (OR 1.46, 95% CI 0.97-2.18, p = 0.066). Three-months and 1-year UC rates were significantly lower in patients with previous LUTS/BPE surgery (OR 0.48, 95% CI 0.34-0.68, p < 0.001 and OR 0.44, 95% CI 0.31-0.62, p < 0.001; respectively). Although not statistically significant differences between the two groups emerged in terms of adoption of NS procedures (OR 0.59, 95% CI 0.32-1.12, p = 0.107), 1-year EF recovery was significantly lower in patients with history of LUTS/BPE procedures (OR 0.60, 95% CI 0.40-0.89, p = 0.010). CONCLUSIONS: In conclusions, RP in patients with history of previous LUTS/BPE surgery is associated with increased incidence of PSM, lower UC rates at both 3-months and 1-year follow-up as well as lower rates of EF recovery at 1-year follow-up.

Photochemical Deracemization of 3-Substituted Oxindoles.

Racemic 3-substituted oxindoles were successfully converted into enantiomerically pure or enriched material (up to 99 % ee) upon irradiation at λ=366 nm in the presence of a chiral benzophenone catalyst (10 mol %). The photochemical deracemization process allows predictable editing of the stereogenic center at carbon atom C3. Light energy compensates for the associated loss of entropy and enables the decoupling of potentially reversible reactions, i.e. a hydrogen atom transfer to (photochemical) and from (thermal) the carbonyl group of the catalyst. The major enantiomer is continuously enriched in several catalytic cycles. The obtained oxindoles were shown to be valuable intermediates for further transformations, which proceeded with complete retention at the stereogenic center.

[Aquablation Treatment for Benign Prostatic Obstruction]. / Aquablation®-Therapie bei der benignen Prostatahyperplasie (BPH).

Aquablation Treatment for Benign Prostatic Obstruction Abstract: The surgical BPH treatment is one of the most common urological procedures. With our reference methods: transurethral resection of the prostate (TUR-P), open surgical adenomenucleation over a transabdominal access, and also modern laser procedures. Various effective surgical options are available. However, the quality of the surgical outcome is highly dependent on the surgeons' experience. At the same time, all of the above-mentioned reference methods are associated with a high rate of sexual dysfunction, especially postoperative anejaculation, a symptom complex which is relevant for men, regardless of age [1]. Robotic Aquablation® was developed with the goal to reduce the dependency of the surgical outcome on the expertise of the surgeon, but at the same time achieving a comparable outcome and reduced morbidity. After the "first in human treatment" by Peter Gilling in 2013, the Aquabeam® robot has been used in its current form in clinical studies since 2015 (Water, Water II and Open Water Study) and finally was introduced in clinical routine in August 2017 by Thorsten Bach in Hamburg. The safety and effectiveness of Aquablation® therapy has been proven in various studies and in everyday clinical practice.

Multifaceted View on the Mechanism of a Photochemical Deracemization Reaction.

Upon irradiation in the presence of a chiral benzophenone catalyst (5 mol %), a racemic mixture of a given chiral imidazolidine-2,4-dione (hydantoin) can be converted almost quantitatively into the same compound with high enantiomeric excess (80-99% ee). The mechanism of this photochemical deracemization reaction was elucidated by a suite of mechanistic experiments. It was corroborated by nuclear magnetic resonance titration that the catalyst binds the two enantiomers by two-point hydrogen bonding. In one of the diastereomeric complexes, the hydrogen atom at the stereogenic carbon atom is ideally positioned for hydrogen atom transfer (HAT) to the photoexcited benzophenone. Detection of the protonated ketyl radical by transient absorption revealed hydrogen abstraction to occur from only one but not from the other hydantoin enantiomer. Quantum chemical calculations allowed us to visualize the HAT within this complex and, more importantly, showed that the back HAT does not occur to the carbon atom of the hydantoin radical but to its oxygen atom. The achiral enol formed in this process could be directly monitored by its characteristic transient absorption signal at λ ≅ 330 nm. Subsequent tautomerization leads to both hydantoin enantiomers, but only one of them returns to the catalytic cycle, thus leading to an enrichment of the other enantiomer. The data are fully consistent with deuterium labeling experiments and deliver a detailed picture of a synthetically useful photochemical deracemization reaction.

Photochemical Ring Contraction of 5,5-Dialkylcyclopent-2-enones and in situ Trapping by Primary Amines.

If substituted in the 5,5-position, cyclopent-2-enones undergo a smooth photochemical rearrangement to ketenes. A concomitant cyclopropane formation occurs due to a 1,3-shift of the C5 carbon atom from the carbonyl carbon atom (C1) to carbon atom C3. In this study, the cyclopropyl-substituted ketene intermediates were trapped in situ by primary amines providing an efficient entry into 2,2-disubstituted cyclopropaneacetic amides (24 examples, 49-95% yield). A remarkable feature of the reaction is the fact that the photochemical rearrangement can occur from either the first excited singlet (S1) or the respective triplet state (T1). In line with experimental results (triplet quenching, sensitization), XMS-CASPT2 calculations support the existence of efficient reaction pathways to the intermediate ketene both on the singlet and on the triplet hypersurface.

Bicyclo[2.1.1]hexanes by Visible Light-Driven Intramolecular Crossed [2 + 2] Photocycloadditions.

Bicyclo[2.1.1]hexanes have become increasingly popular building blocks in medicinal chemistry as bridged scaffolds that provide unexplored chemical space. We herein report a visible light-driven approach to these compounds that relies on an intramolecular crossed [2 + 2] photocycloaddition of styrene derivatives enabled by triplet energy transfer. Bicyclo[2.1.1]hexanes were obtained in good to high yields (19 examples, 61%-quantitative yield) and allowed for further functionalizations by consecutive reactions, thereby opening different pathways to decorate the aliphatic core structure.

Chiral Lewis acid catalysis in a visible light-triggered cycloaddition/rearrangement cascade.

Cascade (domino) reactions facilitate the formation of complex molecules from simple starting materials in a single operation. It was found that 1-naphthaldehyde derivatives can be converted to enantioenriched (82-96% ee) polycyclic benzoisochromenes via a cascade of ortho photocycloaddition and ensuing acid-catalysed rearrangement reactions. The cascade was initiated by irradiation with visible light (λ = 457 nm) and catalysed by a chiral AlBr3-activated 1,3,2-oxazaborolidine (14 examples, 65-93% yield). The absolute configuration of the products was elucidated by single crystal X-ray crystallography. Mechanistic experiments suggest that the ortho photocycloaddition occurs on the triplet hypersurface and that the chiral catalyst induces in this step the observed enantioselectivity.