Structure determination of two new sesquiterpenoids from Streptomyces sanglieri
Sesquiterpenoids are a group of abundant and structurally diverse secondary metabolites mainly derived from plant and fungi. By contrast, they are rarely isolated from bacteria, and the terpene synthase genes had been considered to be silent in prokaryotes. Recently, more and more terpenes were identified from bacteria, and the biosynthesis of some terpenes has been discussed in heterologous bacteria. Actually, it demonstrated that the terpene synthases are widely distributed in bacteria, including streptomycete, and some new sesquiterpenoids and diterpenoids had been obtained through heterologous expression of terpene synthase genes derived from Streptomyces microorganism. In our ongoing investigation of new bioactive natural products from streptomycete, two new sesquiterpenes, 15-hydroxy-(+)-epicubenol (1) and 7β-hydroxy-7-epi-α-eudesmol (2), were identified from a fermentation broth of Streptomyces sanglieri (YIM 121209-2), which was isolated from the forest soil sample collected from Wuyi Mountain, Fujian Province, China. The structures of compounds 1 and 2 (Fig. 1) were elucidated based on detailed spectroscopic data analyses, including 1D and 2D NMR techniques. The cytotoxicity against two human cancer cell lines and antimicrobial activity against a panel of bacteria and fungi of 1 and 2 were evaluated. None of them showed cytotoxic or antimicrobial activities at 100μg/ml.
Essential oil of Amyris balsamifera.
Abstract The essential oil composition of Amyris balsamifera was investigated by GC-MS. Major constituents were separated by fractional distillation and various chromatographic techniques, and identified by mass, 1 H and 13 C NMR spectroscopy and/or chemical reactions. The oil consisted of 17.5% sesquiterpene hydrocarbons and 82.5% oxygenated sesquiterpenes. Major compounds were β-sesquiphellandrene, elemol, 10- epi -γ-eudesmol, γ-eudesmol, valerianol, α-eudesmol, 7- epi -α-eudesmol and β-eudesmol. 7- epi -α-Eudesmol is reported for the first time as a natural product.
Total synthesis of bafilomycin A1.
products. In addition to its broad antibacterial and antifungal activity, the ability of bafilomycin A1 to selectively inhibit V-type ATPases has attracted the most attention, leading to SAR studies and evaluation of its potential for the treatment of diseases, such as osteoporosis. The continued interest in this class of molecules and the need for biologically active analogues demand new synthetic approaches. Moreover, a compex structure such as bafilomycin A1 provides a forum to examine new methods and consequently implement novel tactics. Herein, we disclose an efficient synthesis that showcases the convergent coupling of complex fragments 4 and 5 (Scheme 1) through a zincmediated acetylide addition reaction, and stereoselective reduction of the ensuing enyne moiety by a sequence consisting of a ruthenium-catalyzed trans-hydrosilylation and subsequent protodesilylation. Several total syntheses of bafilomycin A1 have been reported, as well as related methodology studies. These generally showcase the application of established methods for polyketide synthesis. We were motivated to craft a different, complementary strategy to bafilomycin A1 through the implementation of recently developed methods. These include diastereoselective, magnesium-mediated nitrile oxide cycloadditions with chiral allylic alcohols, diastereoselective aldehyde addition reactions of zinc-enealkynilides, and alkyne semireduction (Scheme 1). We envisioned that a successful enyne + RCHO addition reaction would enable a highly efficient fragment–coupling step. However, this approach would only be relevant to the success of the larger synthesis objective if the densely functionalized product enyne could be used to access the trans,trans-1,3diene system found in 1. The synthesis of the C1–C13 fragment (4 ; Scheme 2) commenced with the allylation reaction of 6 with bromide 7 to afford 8 in 87% yield and 97:3 d.r. Reductive cleavage of the auxiliary provided an intermediate alcohol (87% yield), which after Dess–Martin oxidation furnished aldehyde 9 in 99% yield. An anti-selective Masamune aldol addition of 9 with 10 led to b-hydroxy ester 11 as a single diastereoisomer (90 % yield). After silylation (98 % yield) and ester reduction (95 % yield), oxidation of the resulting primary alcohol was followed by Wittig olefination to provide enoate 13 (87 %, over 2 steps). Conversion of ester 13 into aldehyde 14 was accomplished by a sequence involving reduction of the ester group to give an intermediate alcohol (98% yield), Sonogashira cross-coupling with TMSC CH (96 % yield), and oxidation (94 % yield). Subsequent Horner–Wadsworth– Emmons condensation involving 14 gave an intermediate dienoate (> 95:5 d.r.), which after chemoselective alkyne desilylation (96 % yield, over 2 steps) afforded the targeted C1–C13 fragment 4. The synthesis of the C14–C20 fragment (5 ; Scheme 3) centered on the use of a nitrile oxide cycloaddition directed by a hydroxy group, which involved the nitrile oxide derived from oxime 15 and dipolarophile 16. After in situ generation of the nitrile oxide, its cycloaddition with 16 furnished isoxazoline 17 in 74 % yield and > 95:5 d.r. Removal of the trityl protecting group (92 % yield) and protection of the resulting diol as the carbonate using triphosgene (97 % yield) was followed by reductive cleavage of the isoxazoline with Raney-Ni/B(OH)3, [21] to furnish hydroxy ketone 18 in 88% yield. Its subsequent reduction with Me4NBH(OAc)3 resulted in the anti relationship of the alcohols at C15 and C17. Formation of the acetonide was Scheme 1. Retrosynthetic analysis of bafilomycin A1. TBDPS= tertbutyldiphenylsilyl, TBS = tert-butyldimethylsilyl, TES = triethylsilyl.