Studies on the Biomimetic Synthesis of Marine Ladder Polyethers via Endo-Selective Epoxide-to-Epoxonium Ring-Opening Cascades.

Marine ladder polyethers have attracted the attention of chemists and biologists because of their potent biological activities. Synthetic chemists have attempted to construct their polyether frameworks by epoxide ring-opening cascades, as Nakanishi hypothesis describes. However, Baldwin's rules of ring closure state that exo-selective intramolecular cyclization of epoxy alcohols is preferred over endo-selective cyclization. Herein, we investigated epoxide ring-opening cascades of polyepoxy alcohols in [EMIM]BF4/PFTB (1-ethyl-3-methylimidazolium tetrafluoroborate /perfluoro-tert-butyl alcohol) and found that all-endo products were formed via epoxide-to-epoxonium ring-opening cyclizations (not restricted by Baldwin's rules, which only apply to intramolecular hydroxyl-to-epoxide cyclizations). We determined that the key factor enabling polyepoxy alcohols to undergo a high proportion of all-endo-selective cyclization was inhibition of exo-selective hydroxyl-to-epoxide cyclization starting from the terminal hydroxyl group of a polyepoxy alcohol. By introducing a slow-release protecting group to the terminal hydroxyl group, we could markedly increase the cyclization yields of polyether fragments with hydrogen atoms at the ring junctions. For the first time, we constructed consecutively fused six-membered-ring and fused seven-, eight-, and nine-membered-ring polyether fragments by epoxide-to-epoxonium ring-opening cyclizations through the addition of a suitable Lewis acid. We also suggest that the biosynthesis of marine ladder polyethers may proceed via epoxide-to-epoxonium ring-opening cyclization of polyepoxide.

Selective multifunctionalization of N-heterocyclic carbene boranes via the intermediacy of boron-centered radicals.

The selective difunctionalization of N-heterocyclic carbene (NHC) boranes with alkenes has been achieved via decatungstate and thiol synergistic catalysis. The catalytic system also allows stepwise trifunctionalization, leading to complex NHC boranes with three different functional groups which are challenging to prepare by other methods. The strong hydrogen-abstracting ability of the excited decatungstate enables the generation of boryl radicals from mono- and di-substituted boranes for realizing borane multifunctionalization. This proof-of-principle research provides a new chance for fabricating unsymmetrical boranes and developing boron-atom-economic synthesis.

A randomized sham-controlled trial of manual acupuncture for infertile women with polycystic ovary syndrome.

BACKGROUND: Polycystic ovary syndrome (PCOS) is a complex polygenic disease and is one of the most common endocrinological and reproductive disorders. The purpose of this study was to evaluate the efficacy of acupuncture combined with herbal medicine among infertile females with polycystic ovary syndrome (PCOS). METHOD: A total of 86 women with PCOS, experiencing infertility, were recruited and randomly assigned to receive either manual acupuncture (MA) or sham acupuncture (SA) twice per week for three menstrual cycles. Both groups received herbal medication. The evaluations were conducted after three menstrual cycles and 24 weeks' follow-up. RESULTS: The trial was completed by 79 (91.86%) of the 86 randomly selected patients. During this study, the pregnancy rate in the MA group (46.34%) was significantly higher than the SA group (18.42%), with a P-value of 0.008. Moreover, the ovulation rate of the MA group (58.14%) was higher than that of the SA group (45.74%), with a P-value of 0.046. The improvement rate of PCOS score and testosterone level showed a statistical difference between the two groups (P-values were <0.05). There were no other differences between the two groups. Sex hormones level, including E2, T, P, LH, and LH/FSH were significantly lower after intervention in the MA group (P-values were <0.05) compared with baseline, while only the progesterone level was reduced in the SA group (P-value = 0.008). CONCLUSION: Manual acupuncture combined with herbal medicine may be clinically useful for infertile women with PCOS in improving pregnancy and ovulation rate. TRIAL REGISTRATION: Chinese Clinical Trial Registry: ChiCTR1800014997.

An Endo-Selective Epoxide-Opening Cascade for the Fast Assembly of the Polycyclic Core Structure of Marine Ladder Polyethers.

The rapid synthesis of marine ladder polyethers from polyepoxide precursors (in analogy with the biosynthetic pathway hypothesized by Nakanishi) is hampered by the fact that the exo-selective epoxide-opening cyclization cascade that gives THF-type polyethers is preferred over the endo-selective cascade that gives the desired products. We found that perfluoro-tert-butanol (PFTB) cooperating with 1-ethyl-3-methylimidazolium tetrafluoroborate ([EMIM]BF4 ) can promote endo-selective epoxide-opening cyclization reactions of trisubstituted epoxy alcohols. Starting from readily accessible homochiral polyepoxy alcohols with a methyl group at all the endo-cyclization sites, we were able to construct polyethers up to five consecutive fused 6-, 7-, and/or 8-membered rings in one step. Notably, molecules with the 7/7/6/6 and 7/7/6/7/6 polyether frameworks of hemibrevetoxin B and brevenal, respectively, could be synthesized in 40 % and 17 % chemical yields.

Asymmetric formal synthesis of (+)-cycloclavine.

The asymmetric synthesis of Szántay's amine (+)-2, the pivotal precursor for direct access to (+)-cycloclavine (1), is described for the first time in eleven steps with 19.7% overall yield from the commercially available 4-bromoindole. The strategy features an asymmetric induction by Ellman's sulfinimine and rhodium-catalysed isomerization of the C[double bond, length as m-dash]C bond.