Ultrasound-on-chip platform for medical imaging, analysis, and collective intelligence.

Over the past half-century, ultrasound imaging has become a key technology for assessing an ever-widening range of medical conditions at all stages of life. Despite ultrasound's proven value, expensive systems that require domain expertise in image acquisition and interpretation have limited its broad adoption. The proliferation of portable and low-cost ultrasound imaging can improve global health and also enable broad clinical and academic studies with great impact on the fields of medicine. Here, we describe the design of a complete ultrasound-on-chip, the first to be cleared by the Food and Drug Administration for 13 indications, comprising a two-dimensional array of silicon-based microelectromechanical systems (MEMS) ultrasonic sensors directly integrated into complementary metal-oxide-semiconductor-based control and processing electronics to enable an inexpensive whole-body imaging probe. The fabrication and design of the transducer array with on-chip analog and digital circuits, having an operating power consumption of 3 W or less, are described, in which approximately 9,000 seven-level feedback-based pulsers are individually addressable to each MEMS element and more than 11,000 amplifiers, more than 1,100 analog-to-digital converters, and more than 1 trillion operations per second are implemented. We quantify the measured performance and the ability to image areas of the body that traditionally takes three separate probes. Additionally, two applications of this platform are described-augmented reality assistance that guides the user in the acquisition of diagnostic-quality images of the heart and algorithms that automate the measurement of cardiac ejection fraction, an indicator of heart health.

FastGrow: on-the-fly growing and its application to DYRK1A.

Fragment-based drug design is an established routine approach in both experimental and computational spheres. Growing fragment hits into viable ligands has increasingly shifted into the spotlight. FastGrow is an application based on a shape search algorithm that addresses this challenge at high speeds of a few milliseconds per fragment. It further features a pharmacophoric interaction description, ensemble flexibility, as well as geometry optimization to become a fully fledged structure-based modeling tool. All features were evaluated in detail on a previously reported collection of fragment growing scenarios extracted from crystallographic data. FastGrow was also shown to perform competitively versus established docking software. A case study on the DYRK1A kinase, using recently reported new chemotypes, illustrates FastGrow's features in practice and its ability to identify active fragments. FastGrow is freely available to the public as a web server at https://fastgrow.plus/ and is part of the SeeSAR 3D software package.

Wound of the Parotid Duct Following a Subcondylar Fracture.

Salivary gland and duct complications following surgical approaches to condylar fractures are well known, particularly in approaches requiring parotid tissue dissection. We report a rare case of a parotid duct wound caused by the fracture itself and due to a lateral displacement of the condylar fragment. Four days after the surgical management of a trifocal mandibular fracture (head fracture on the left side, laterally displaced condylar base and angular fracture on the right side) the patient presented with a fluctuating subcutaneous swelling in the right cheek, evoking a sialocele. The sialography showed a massive leak of iodinated contrast medium just in front of the parotid hilum, joining the subcutaneous undermining made during the approach and confirmed the diagnosis of a parotid duct wound. A pressure dressing was applied to the right mandibular angle for 2 weeks, allowing for complete remission. In conclusion, this unusual clinical case illustrates the fact that the parotid duct may be endangered in the event of condylar base fractures, not only by the surgical approach but also by the fracture itself, especially when there is severe lateral displacement.

Improved Lipophilicity and Aqueous Solubility Prediction with Composite Graph Neural Networks.

The accurate prediction of molecular properties, such as lipophilicity and aqueous solubility, are of great importance and pose challenges in several stages of the drug discovery pipeline. Machine learning methods, such as graph-based neural networks (GNNs), have shown exceptionally good performance in predicting these properties. In this work, we introduce a novel GNN architecture, called directed edge graph isomorphism network (D-GIN). It is composed of two distinct sub-architectures (D-MPNN, GIN) and achieves an improvement in accuracy over its sub-architectures employing various learning, and featurization strategies. We argue that combining models with different key aspects help make graph neural networks deeper and simultaneously increase their predictive power. Furthermore, we address current limitations in assessment of deep-learning models, namely, comparison of single training run performance metrics, and offer a more robust solution.

Evaluation modalities for the anatomical repair of chronic ankle instability.

PURPOSE: Several evaluation modalities are reported in the literature dealing with the operative treatment of chronic ankle instability (CAI) both to establish the CAI diagnosis leading to the surgical indication and to assess the effectiveness of ankle stabilisation procedure. The purpose of this study is to present an overview of the pre- and postoperative evaluation modalities reported in the literature dealing with CAI operative treatment. The comprehensive analysis of the different modalities chosen by researchers is expected to suggest critical points in current evaluation ability of CAI surgical treatment. METHODS: Systematic review of the literature on surgical treatment of CAI through anatomic procedures. Pubmed, Embase and Cochrane electronic databases were analysed, from 2004 to 2018. RESULTS: One-hundred-and-four studies met inclusion in this systematic review. 88 out of 104 studies analysed preoperative mechanical laxity of the ankle to depict the ligamentous insufficiency related to the subjective feeling of functional instability. Stress radiographs and manual stress examination of the ankle were the two most common modalities to evaluate joint laxity, reported in 67 and 53 studies, respectively. Clinical Outcome Measurement Scales (COMs) is the most common evaluation modality (102 out of 104 studies) to assess CAI surgical outcome. The American Orthopaedic Foot and Ankle Society Ankle-Hindfoot scale (AOFAS) and the Karlsson score are the most frequent COMs, reported in the 66% and 33%, respectively of the included literature. The radiographic analysis of ankle laxity after stabilisation procedures is the second most frequent postoperative evaluation modality, reported in 55 out 104 studies. CONCLUSIONS: There is a lack of standardization among researchers related to both the criteria to establish the CAI diagnosis leading to the surgical indication and the modality chosen to evaluate the effectiveness of surgical treatment. Future standardization of evaluation modalities in the CAI population is desirable to increase consistency of reported data. LEVEL OF EVIDENCE: Level IV, review of level I, II, III and IV studies.

Management of maxillofacial trauma in the elderly: A European multicenter study.

BACKGROUND/AIMS: Management of maxillofacial trauma in the geriatric population poses a great challenge due to anatomical variations and medical comorbidities. The aim of this study was to analyze the management variables, timing, and outcomes of facial fractures in elderly patients (aged 70 years or more) at several European departments of oral and maxillofacial surgery. MATERIALS AND METHODS: This study was based on a systematic computer-assisted database that allowed the recording of data from all geriatric patients with facial fractures from the involved maxillofacial surgical units across Europe between 2013 and 2017. RESULTS: A total of 1334 patients were included in the study: 665 patients underwent closed or open surgical treatment. A significant association (P < .005) was found between the presence of concomitant injuries and a prolonged time between hospital admission and treatment. The absence of indications to treatment was associated with comorbidities and an older age (P < .000005). CONCLUSIONS: Elderly patients require specific attention and multidisciplinary collaboration in the diagnosis and sequencing of trauma treatment. A prudent attitude may be kept in selected cases, especially when severe comorbidities are associated and function is not impaired.

Comparative Assessment of Protein Kinase Inhibitors in Public Databases and in PKIDB.

Since the first approval of a protein kinase inhibitor (PKI) by the Food and Drug Administration (FDA) in 2001, 55 new PKIs have reached the market, and many inhibitors are currently being evaluated in clinical trials. This is a clear indication that protein kinases still represent major drug targets for the pharmaceutical industry. In a previous work, we have introduced PKIDB, a publicly available database, gathering PKIs that have already been approved (Phase 4), as well as those currently in clinical trials (Phases 0 to 3). This database is updated frequently, and an analysis of the new data is presented here. In addition, we compared the set of PKIs present in PKIDB with the PKIs in early preclinical studies found in ChEMBL, the largest publicly available chemical database. For each dataset, the distribution of physicochemical descriptors related to drug-likeness is presented. From these results, updated guidelines to prioritize compounds for targeting protein kinases are proposed. The results of a principal component analysis (PCA) show that the PKIDB dataset is fully encompassed within all PKIs found in the public database. This observation is reinforced by a principal moments of inertia (PMI) analysis of all molecules. Interestingly, we notice that PKIs in clinical trials tend to explore new 3D chemical space. While a great majority of PKIs is located on the area of "flatland", we find few compounds exploring the 3D structural space. Finally, a scaffold diversity analysis of the two datasets, based on frequency counts was performed. The results give insight into the chemical space of PKIs, and can guide researchers to reach out new unexplored areas. PKIDB is freely accessible from the following website: http://www.icoa.fr/pkidb.

Asymmetric Transfer Hydrogenation of gem-Difluorocyclopropenyl Esters: Access to Enantioenriched gem-Difluorocyclopropanes.

Catalytic enantioselective access to disubstituted functionalized gem-difluorocyclopropanes, which are emerging fluorinated motifs of interest in medicinal chemistry, was achieved through asymmetric transfer hydrogenation of gem-difluorocyclopropenyl esters, catalyzed by a Noyori-Ikariya (p-cymene)-ruthenium(II) complex, with (N-tosyl-1,2-diphenylethylenediamine) as the chiral ligand and isopropanol as the hydrogen donor. The resulting cis-gem-difluorocyclopropyl esters were obtained with moderate to high enantioselectivity (ee=66-99 %), and post-functionalization reactions enable access to valuable building blocks incorporating a cis- or trans-gem-difluorocyclopropyl motif.

Assembly of the Entire Carbon Backbone of a Stereoisomer of the Antitumor Marine Natural Product Hemicalide.

A strategy for the assembly of the entire carbon backbone of a stereoisomer of the antitumor marine natural product hemicalide has been investigated. The devised convergent approach relies on Horner-Wadsworth-Emmons and Julia-Kocienski olefination reactions for the construction of the C6=C7 and C34=C35 double bonds, respectively, an aldol reaction to create the C27-C28 bond, and a Suzuki-Miyaura cross-coupling as the endgame to form the C15-C16 bond.

In vitro osteodifferentiation of intact human amniotic membrane is not beneficial in the context of bone repair.

The human amniotic membrane (hAM) is an attractive biomaterial for regenerative medicine, as it contains amniotic mesenchymal stromal cells (hAMSC), epithelial cells (hAEC) and growth factors. We examined the potential use of hAM in orthopaedic and maxillofacial bone surgery, integrating the requirements of current regulations regarding advanced therapy medicinal products (ATMP) in the European Union. Previous studies have described the potential osteodifferentiation of intact hAM during whole-tissue culture in osteogenic conditions. The present study aims to determine whether in vitro osteodifferentiation of hAM is needed in the context bone repair, and the influence of this process on tissue structure, cell phenotype and cell function. Different conditions (fresh or cultured hAM; intact or hAM-derived cells) were tested. Phenotypic and functional analyses were performed with standard approaches (cell culture and staining, histological and immunolabelling) as well as original approaches (tissue staining, energy dispersive X-ray and X-ray diffraction). In our study, non-osteodifferentiated hAM (i.e., fresh or native hAM) exhibited innate pre-osteoblastic potential. Osteodifferentiation of fresh hAM induced a change in tissue structure, cell phenotype and function. Therefore, we hypothesize that pre-osteodifferentiation may not be necessary, especially if it induces unwanted changes. To our surprise, in these osteogenic conditions, hAEC had a mesenchymal phenotype with osteocyte function, and even native synthesis of hydroxyapatite, focusing osteogenic potential mainly in this epithelial layer. In conclusion, in vitro osteodifferentiation by tissue culture does not appear to be necessary for hAM to be used as an innovative ATMP for bone repair.

Sigmatropic rearrangements of cyclopropenylcarbinol derivatives. Access to diversely substituted alkylidenecyclopropanes.

Cyclopropenes constitute useful precursors of other classes of compounds incorporating a three-membered ring. Although the transformation of substituted cyclopropenes into alkylidenecyclopropanes can be accomplished through different strategies, this review is focusing specifically on the use of [2,3]- and [3,3]-sigmatropic rearrangements involving cyclopropenylcarbinol derivatives as substrates. These sigmatropic rearrangements, which have been developed in recent years, allow a remarkably efficient and stereoselective access to a wide variety of heterosubstituted and/or functionalized alkylidenecyclopropanes which would not be readily accessible by other strategies. The different [2,3]- and [3,3]-sigmatropic rearrangements of cyclopropenylcarbinol derivatives disclosed to date, as well as the analysis of their substrate scope and some applications of the products arising from those reactions, are presented in this review.

[3,3]-Sigmatropic Rearrangement of Cyclopropenylcarbinyl Cyanates: Access to Alkylidene(aminocyclopropane) Derivatives.

Cyclopropenylcarbinyl cyanates, generated in situ by dehydration of the corresponding carbamates, underwent an efficient and stereoselective [3,3]-sigmatropic rearrangement leading to the corresponding alkylidene(isocyanatocyclopropanes), which could be converted into various alkylidene(aminocyclopropane) derivatives in a one-pot manner. This transformation complements the repertoire of sigmatropic rearrangements involving cyclopropenylcarbinol derivatives and in particular, the previously reported Overman rearrangement of cyclopropenylcarbinyl trichloroacetimidates.

Design and synthesis of a series of bioavailable fatty acid synthase (FASN) KR domain inhibitors for cancer therapy.

We designed and synthesized a new series of fatty acid synthase (FASN) inhibitors with potential utility for the treatment of cancer. Extensive SAR studies led to highly active FASN inhibitors with good cellular activity and oral bioavailability, exemplified by compound 34. Compound 34 is a potent inhibitor of human FASN (IC50 = 28 nM) that effectively inhibits proliferation of A2780 ovarian cells (IC50 = 13 nM) in lipid-reduced serum (LRS). This cellular activity can be rescued by addition of palmitate, consistent with an on-target effect. Compound 34 is also active in many other cell types, including PC3M (IC50 = 25 nM) and LnCaP-Vancouver prostate cells (IC50 = 66 nM), and is highly bioavailable (F 61%) with good exposure after oral administration. In a pharmacodynamics study in H460 lung xenograft-bearing mice, oral treatment with compound 34 results in elevated tumor levels of malonyl-CoA and decreased tumor levels of palmitate, fully consistent with the desired target engagement.

Side-to-side asymmetries in landing mechanics from a drop vertical jump test are not related to asymmetries in knee joint laxity following anterior cruciate ligament reconstruction.

PURPOSE: Asymmetries in knee joint biomechanics and increased knee joint laxity in patients following anterior cruciate ligament reconstruction (ACLR) are considered risk factors for re-tear or early onset of osteoarthritis. Nevertheless, the relationship between these factors has not been established. The aim of the study was to compare knee mechanics during landing from a bilateral drop vertical jump in patients following ACLR and control participants and to study the relationship between side-to-side asymmetries in landing mechanics and knee joint laxity. METHODS: Seventeen patients following ACLR were evaluated and compared to 28 healthy controls. Knee sagittal and frontal plane kinematics and kinetics were evaluated using three-dimensional motion capture (200 Hz) and two synchronized force platforms (1000 Hz). Static anterior and internal rotation knee laxities were measured for both groups and legs using dedicated arthrometers. Group and leg differences were investigated using a mixed model analysis of variance. The relationship between side-to-side differences in sagittal knee power/energy absorption and knee joint laxities was evaluated using univariate linear regression. RESULTS: A significant group-by-leg interaction (p = 0.010) was found for knee sagittal plane energy absorption, with patients having 25% lower values in their involved compared to their non-involved leg (1.22 ± 0.39 vs. 1.62 ± 0.40 J kg-1). Furthermore, knee sagittal plane energy absorption was 18% lower at their involved leg compared to controls (p = 0.018). Concomitantly, patients demonstrated a 27% higher anterior laxity of the involved knee compared to the non-involved knee, with an average side-to-side difference of 1.2 mm (p < 0.001). Laxity of the involved knee was also 30% higher than that of controls (p < 0.001) (leg-by-group interaction: p = 0.002). No relationship was found between sagittal plane energy absorption and knee laxity. CONCLUSIONS: Nine months following surgery, ACLR patients were shown to employ a knee unloading strategy of their involved leg during bilateral landing. However, this strategy was unrelated to their increased anterior knee laxity. Side-to-side asymmetries during simple bilateral landing tasks may put ACLR patients at increased risk of second ACL injury or early-onset osteoarthritis development. Detecting and correcting asymmetric landing strategies is highly relevant in the framework of personalized rehabilitation, which calls for complex biomechanical analyses to be applied in clinical routine. LEVEL OF EVIDENCE: III.

PKIDB: A Curated, Annotated and Updated Database of Protein Kinase Inhibitors in Clinical Trials.

The number of protein kinase inhibitors (PKIs) approved worldwide continues to grow steadily, with 39 drugs approved in the period between 2001 and January 2018. PKIs on the market have been the subject of many reviews, and structure-property relationships specific to this class of drugs have been inferred. However, the large number of PKIs under development is often overlooked. In this paper, we present PKIDB (Protein Kinase Inhibitor Database), a monthly-updated database gathering approved PKIs as well as PKIs currently in clinical trials. The database compiles currently 180 inhibitors ranging from phase 0 to 4 clinical trials along with annotations extracted from seven public resources. The distribution and property ranges of standard physicochemical properties are presented. They can be used as filters to better prioritize compound selection for future screening campaigns. Interestingly, more than one-third of the kinase inhibitors violate at least one Lipinski's rule. A Principal Component Analysis (PCA) reveals that Type-II inhibitors are mapped to a distinct chemical space as compared to orally administrated drugs as well as to other types of kinase inhibitors. Using a Principal Moment of Inertia (PMI) analysis, we show that PKIs under development tend to explore new shape territories as compared to approved PKIs. In order to facilitate the analysis of the protein space, the kinome tree has been annotated with all protein kinases being targeted by PKIs. Finally, we analyzed the pipeline of the pharmaceutical companies having PKIs on the market or still under development. We hope that this work will assist researchers in the kinase field in identifying and designing the next generation of kinase inhibitors for still untargeted kinases. The PKIDB database is freely accessible from a website at http://www.icoa.fr/pkidb and can be easily browsed through a user-friendly spreadsheet-like interface.

The use of novel selectivity metrics in kinase research.

BACKGROUND: Compound selectivity is an important issue when developing a new drug. In many instances, a lack of selectivity can translate to increased toxicity. Protein kinases are particularly concerned with this issue because they share high sequence and structural similarity. However, selectivity may be assessed early on using data generated from protein kinase profiling panels. RESULTS: To guide lead optimization in drug discovery projects, we propose herein two new selectivity metrics, namely window score (WS) and ranking score (RS). These metrics can be applied to standard in vitro data-including intrinsic enzyme activity/affinity (Ki, IC50 or percentage of inhibition), cell-based potency (percentage of effect, EC50) or even kinetics data (Kd, Kon and Koff). They are both easy to compute and offer different viewpoints from which to consider compound selectivity. CONCLUSIONS: We performed a comparative analysis of their respective performance on several data sets against already published selectivity metrics and analyzed how they might influence compound selection. Our results showed that the two new metrics bring additional information to prioritize compound selection. Two novel metrics were developed to better estimate selectivity of compounds screened on multiple proteins.

Synthesis of Alkylidene(gem-Difluorocyclopropanes) from Propargyl Glycolates by a One-Pot Difluorocyclopropenation/Ireland-Claisen Rearrangement Sequence.

A one-pot difluorocyclopropenation/Ireland-Claisen rearrangement sequence applied to readily available propargyl glycolates was developed as a route toward functionalized alkylidene(gem-difluorocyclopropanes). This strategy conveniently avoids the isolation of the unstable 3,3-difluorocyclopropenylcarbinyl glycolates arising from the difluorocyclopropenation. The Ireland-Claisen rearrangement proceeds with high diastereoselectivity and chirality transfer to afford alkylidene(gem-difluorocyclopropanes) incorporating a quaternary stereocenter and a protected glycolic acid moiety, which are useful building blocks for the preparation of functionalized gem-difluorocyclopropanes.

Prediction of Protein Kinase-Ligand Interactions through 2.5D Kinochemometrics.

So far, 518 protein kinases have been identified in the human genome. They share a common mechanism of protein phosphorylation and are involved in many critical biological processes of eukaryotic cells. Deregulation of the kinase phosphorylation function induces severe illnesses such as cancer, diabetes, or inflammatory diseases. Many actors in the pharmaceutical domain have made significant efforts to design potent and selective protein kinase inhibitors as new potential drugs. Because the ATP binding site is highly conserved in the protein kinase family, the design of selective inhibitors remains a challenge and has negatively impacted the progression of drug candidates to late-stage clinical development. The work presented here adopts a 2.5D kinochemometrics (KCM) approach, derived from proteochemometrics (PCM), in which protein kinases are depicted by a novel 3D descriptor and the ligands by 2D fingerprints. We demonstrate in two examples that the protein descriptor successfully classified protein kinases based on their group membership and their Asp-Phe-Gly (DFG) conformation. We also compared the performance of our models with those obtained from a full 2D KCM model and QSAR models. In both cases, the internal validation of the models demonstrated good capabilities to distinguish "active" from "inactive" protein kinase-ligand pairs. However, the external validation performed on two independent data sets showed that the two statistical models tended to overestimate the number of "inactive" pairs.

Fresh and in vitro osteodifferentiated human amniotic membrane, alone or associated with an additional scaffold, does not induce ectopic bone formation in Balb/c mice.

The human amniotic membrane (hAM) has been successfully used as a natural carrier containing amniotic mesenchymal stromal cells, epithelial cells and growth factors. It has a little or no immunogenicity, and possesses useful anti-microbial, anti-inflammatory, anti-fibrotic and analgesic properties. It has been used for many years in several indications for soft tissue repair. We previously reported that hAM represents a natural and preformed sheet containing highly potent stem cells, and could thus be used for bone repair. Indeed, native hAM possesses pre-osteoblastic potential that can easily be stimulated, even as far as mineralization, by means of in vitro osteogenic culture. However, cell culture induces damage to the tissue, as well as to cell phenotype and function. The aim of this study was to evaluate new bone formation by fresh and in vitro osteodifferentiated hAM, alone or associated with an additional scaffold presenting osteoinductive properties. Moreover, we also aimed to determine the effect of in vitro hAM pre-osteodifferentiation on its in vivo biocompatibility/tissue degradation. Results showed that neither fresh nor osteodifferentiated hAM induced ectopic bone formation, whether or not it was associated with the osteoinductive scaffold. Secondly, fresh and osteodifferentiated hAM presented similar in vivo tissue degradation, suggesting that in vitro hAM pre-osteodifferentiation did not influence its in vivo biocompatibility.

Intramolecular cyclopropanation and C-H insertion reactions with metal carbenoids generated from cyclopropenes.

Activation of unsaturated carbon-carbon bonds by means of transition metal catalysts is an exceptionally active research field in organic synthesis. In this context, due to their high ring strain, cyclopropenes constitute an interesting class of substrates that displays a versatile reactivity in the presence of transition metal catalysts. Metal complexes of vinyl carbenes are involved as key intermediates in a wide variety of transition metal-catalyzed ring-opening reactions of cyclopropenes. Most of the reported transformations rely on intermolecular or intramolecular addition of nucleophiles to these latter reactive species. This Account focuses specifically on the reactivity of carbenoids resulting from the ring-opening of cyclopropenes in cyclopropanation and C-H insertion reactions, which are arguably two of the most representative transformations of metal complexes of carbenes. Compared with the more conventional α-diazo carbonyl compounds, the use of cyclopropenes as precursors of metal carbenoids in intramolecular cyclopropanation or C-H insertion reactions has been largely underexploited. One of the challenges is to devise appropriately substituted and readily available cyclopropenes that would not only undergo regioselective ring-opening under mild conditions but also trigger the subsequent desired transformations with a high level of chemoselectivity and stereoselectivity. These goals were met by considering several substrates derived from the readily available 3,3-dimethylcyclopropenylcarbinols or 3,3-dimethylcyclopropenylcarbinyl amines. In the case of 1,6-cyclopropene-enes, highly efficient and diastereoselective gold(I)-catalyzed ring-opening/intramolecular cyclopropanations were developed as a route to diversely substituted heterocycles and carbocycles possessing a bicyclo[4.1.0]heptane framework. The use of rhodium(II) catalysts enabled us to widen the scope of this transformation for the synthesis of medium-sized heterocyclic scaffolds incorporating an eight-membered ring. The reactivity of rhodium(II) carbenoids generated from 3,3-dimethylcyclopropenylcarbinols was also investigated in intramolecular C(sp(3))-H insertions. Despite their low electrophilic character, these purely donor rhodium(II) carbenoids underwent remarkably efficient diastereoselective 1,5- or 1,6-C-H insertions allowing access to a wide variety of substituted cyclopentanols, cyclohexanols, bicycloalkanols, and tetrahydropyrans with high level of diastereoselectivity and with complete tolerance of a free hydroxyl group. The products arising from the gold(I)- or rhodium(II)-catalyzed ring-opening/intramolecular cyclopropanation or C-H insertion of 3,3-dimethylcyclopropenylcarbinols or 3,3-dimethylcyclopropenylcarbinyl amines always incorporate an isopropylidene moiety, which can potentially undergo subsequent oxidative cleavage into a carbonyl group without epimerization. By virtue of this operation, the 3,3-dimethylcyclopropenyl group formally behaves as a valuable surrogate for an α-diazoketone, with obvious advantages considering the ease of access to the corresponding substrates and that no hazardous reagents are involved in their preparation. These studies have set a useful basis for the development of other reaction pathways involving metal carbenoids generated from these readily available families of substituted cyclopropenes, including the investigation of the yet underexploited synthetic potential of purely donor rhodium(II) carbenoids.