Highly Regio-, Stereo-, and Enantioselective Copper-Catalyzed B-H Bond Insertion of α-Silylcarbenes: Efficient Access to Chiral Allylic gem-Silylboranes.

Herein, we report the development of a method for highly regio-, stereo-, and enantioselective B-H bond insertion reactions of α-silylcarbenes generated from 1-silylcyclopropenes in the presence of a chiral copper(I)/bisoxazoline catalyst for the construction of chiral γ,γ-disubstituted allylic gem-silylboranes, which cannot be prepared by any other known methods. This reaction is the first highly enantioselective carbene insertion reaction of α-silylcarbenes ever to be reported. The method shows general applicability for various 3,3-disubstituted silylcyclopropenes and exclusively affords E-products. The novel chiral γ,γ-disubstituted allylic gem-silylborane products are versatile allylic bimetallic reagents with high stability and have great synthetic potential, especially for the construction of complex molecules with continuous chiral centers.

Dirhodium-Catalyzed Enantioselective B-H Bond Insertion of gem-Diaryl Carbenes: Efficient Access to gem-Diarylmethine Boranes.

The scarcity of reliable methods for synthesizing chiral gem-diarylmethine borons limits their applications. Herein, we report a method for highly enantioselective dirhodium-catalyzed B-H bond insertion reactions with diaryl diazomethanes as carbene precursors. These reactions afforded chiral gem-diarylmethine borane compounds in high yield (up to 99 % yield), high activity (turnover numbers up to 14 300), high enantioselectivity (up to 99 % ee) and showed unprecedented broad functional group tolerance. The borane compounds synthesized by this method could be efficiently transformed into diaryl methanol, diaryl methyl amine, and triaryl methane derivatives with good stereospecificity. Mechanistic studies suggested that the borane adduct coordinated to the rhodium catalyst and thus interfered with decomposition of the diazomethane, and that insertion of a rhodium carbene (generated from the diaryl diazomethane) into the B-H bond was most likely the rate-determining step.

Insertion of Alkylidene Carbenes into B-H Bonds.

We have developed a protocol for insertion of alkylidene carbenes into the B-H bonds of amine-borane adducts, enabling, for the first time, the construction of C(sp2)-B bonds by means of carbene-insertion reactions. Various acyclic and cyclic alkenyl borane-amine adducts were prepared from readily accessible starting materials in good to high yields and were subsequently subjected to a diverse array of functional group transformations. The unprecedented spiro B-N heterocycles prepared in this study have potential utility as building blocks for the synthesis of pharmaceuticals. Preliminary mechanistic studies suggest that insertion of the alkylidene carbenes into the B-H bonds of the amine-borane adducts proceeds via a concerted process involving a three-membered-ring transition state.

Highly Enantioselective O-H Bond Insertion Reaction of α-Alkyl- and α-Alkenyl-α-diazoacetates with Water.

Catalytic asymmetric reactions in which water is a substrate are rare. Enantioselective transition-metal-catalyzed insertion of carbenes into the O-H bond of water can be used to incorporate water into the stereogenic center, but the reported chiral catalysts give good results only when α-aryl-α-diazoesters are used as the carbene precursors. Herein we report the first highly enantioselective O-H bond insertion reactions between water and α-alkyl- and α-alkenyl-α-diazoesters as carbene precursors, with catalysis by a combination of achiral dirhodium complexes and chiral phosphoric acids or chiral phosphoramides. Participation of the phosphoric acids or phosphoramides in the carbene transfer reaction markedly suppressed competing side reactions, such as ß-H migration, carbene dimerization, and olefin isomerization, and thus ensured good yields of the desired products. Fine-tuning of the ester moiety facilitated enantiocontrol of the proton transfer reactions of the enol intermediates and resulted in excellent enantioselectivity. This protocol represents an efficient new method for preparation of multifunctionalized chiral α-alkyl and α-alkenyl hydroxyl esters, which readily undergo various transformations and can thus be used for the synthesis of bioactive compounds. Mechanistic studies revealed that the phosphoric acids and phosphoramides promoted highly enantioselective [1,2]- and [1,3]-proton transfer reactions of the enol intermediates. Maximization of molecular orbital overlap in the transition states of the proton transfer reactions was the original driving force to involve the proton shuttle catalysts in this process.

[Bushen Huoxue Recipe reduces cyclophosphamide-induced apoptosis of spermatogenic cells in mice].

OBJECTIVE: To investigate the effect of Bushen Huoxue Recipe (BHR) on cyclophosphamide-induced apoptosis of testicular spermatogenic cells in mice and its possible action mechanisms. METHODS: Fifty male Babl/c mice aged 8－9 weeks were randomly divided into five groups of an equal number: blank control, model control, low-dose BHR, medium-dose BHR and high-dose BHR. The animals in the blank control group were intraperitoneally injected with normal saline, while those in the other four groups with cyclophosphamide at 50 mg/kg/d, all for 7 days. After modeling, the mice in the blank and model control groups were given distilled water via gavage once a day, and those in the low-, medium- and high-dose BHR groups treated intragastrically with BHR at 7.5, 15 and 30 g/kg/d qd for 30 successive days. Then, the apoptosis index of the testicular spermatogenic cells was obtained by TUNEL and the expressions of Bax and Bcl-2 mRNA and proteins determined by RT-PCR and Western blot, respectively. RESULTS: Compared with the mice in the blank control group, the BHR model controls showed dramatically increased apoptosis of testicular spermatogenic cells and up-regulated mRNA and protein expressions of Bax and Bcl-2 in the testis tissue (P < 0.01). In comparison with the model controls, the mice in the BHR treatment groups exhibited significantly reduced apoptosis of testicular spermatogenic cells and down-regulated mRNA and protein expressions of Bax and Bcl-2 in the testis tissue (P < 0.01). CONCLUSIONS: Bushen Huoxue Recipe can reduce cyclophosphamide-induced apoptosis of testicular spermatogenic cells in mice, which may be associated with its ability of regulating the expressions of Bax and Bcl-2 mRNA and proteins in the testis tissue.

Efficacy and safety of letrozole or anastrozole in the treatment of male infertility with low testosterone-estradiol ratio: A meta-analysis and systematic review.

BACKGROUND: Aromatase inhibitors (AIs) have been used to treat male infertility for decades. However, due to the lack of large-scale randomized controlled studies and basic research, the efficacy and safety of AIs in the treatment of male infertility remain controversial. Therefore, it is necessary to conduct an evidence-based preliminary evaluation of the existing clinical trials of AIs in the treatment of male infertility. METHOD: A comprehensive literature search was performed in the PubMed, Embase, Cochrane, CNKI, VIP, CBM, and Wanfang databases through August 2021 for all studies. We conducted a systematic review with a meta-analysis of all available studies reporting sperm conventional parameters, gonadotropin and testosterone levels, and/or the pregnancy rate. RESULTS: A total of 10 studies involving 666 patients were included. Letrozole (LE) or anastrozole (AZ) administration significantly increased sperm concentration, total sperm count, serum luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone (T) levels, and the testosterone-to-estradiol ratio (T/E2), but E2 levels were significantly reduced compared with baseline values. Compared with the control group, which included selective estrogen receptor modulators (SEMRs) or human chorionic gonadotropin (HCG), LE, or AZ did not have any significant effect on sperm concentration, motility, and morphology, except that AIs had less effect on sperm motility than the control group (weighted mean difference [WMD]: -2.55; 95% CI: -4.11 to -1.00; p = 0.001). CONCLUSION: AIs may be effective in the treatment of male infertility. For infertile male patients planning assisted reproduction, discontinuation of AIs for 2-7 days prior to sperm retrieval may increase the success rate of fertilization. Further studies with larger sample sizes are needed to validate these findings.

An efficient and convenient formal synthesis of Jaspine B from D-xylose.

A formal synthesis of Jaspine B was completed in 42.4% overall yield with only three purification steps (one by crystallization and two by column chromatography). The key step in the synthesis involves a regio- and stereoselective epoxide ring-opening reaction and the configuration inversion of the C3-hydroxyl group through oxidation and reduction. All of the reagents and materials used were quite common and inexpensive.

[Soil enzyme activities under two forest types as affected by different levels of nitrogen deposition].

A simulation test was conducted to study the change trends of soil cellulase, polyphenol oxidase, and sucrase activities under natural broadleaf-Korean pine (Pinus koraiensis) and secondary poplar (Populus davidiana) -birch (Betula platyphylla) mixed forests as affected by 0, 25, and 50 kg x hm(-2) x a(-1) of N deposition. The results showed that the effects of elevated N deposition on test enzyme activities varied with forest type, and short-term nitrogen addition could significantly affect the test enzyme activities. High N deposition decreased soil polyphyneol oxidase activity, and correspondingly, soil cellulase and sucrase activities also had a trend of decrease.

[Decomposition of litter organic matter and its relations to C, N and P release in secondary conifer and broadleaf mixed forest in Changbai Mountains].

By using litterbag method, the decomposition processes of 9 types of foliar litter in secondary conifer and broadleaf mixed forest in Changbai Mountains were assessed during a period of 34 months. The initial N and P concentrations varied greatly among the litters, and there were significant relationships between litter decomposition constant (k) and initial N concentration and C/N. The percent organic matter remaining had a significant linear correlation with percent C remaining, and a significant polynomial correlation with percent N and P remaining. The percent N and P remaining increased with the decomposition of organic matter in its initial decomposition phase, but decreased gradually in the latter decomposition phase. C/N and C/P declined with the decrease of percent organic matter remaining, and the differences in C/N or C/P among litter types decreased, being approached to 23 and 350, respectively by the end of the study. During organic matter decomposition, N/P did not change greatly, and the differences in N/P between litter types declined when the percent organic matter remaining was below 25%. Our study showed that percent of C, N and P mass remaining can be predicted by percent of organic matter mass remaining.