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The first stereoselective synthesis of the C1−C16 fragment possessing stereo-enriched fully substituted tetrahydropyran (THP) along with tetrahydrofuran (THF) rings of the proposed structure of formosalide B is described in 12 longest linear steps with 22% overall yield, starting from two cheap and commercially available 1,5-pentanediol and L-glutamic acid, following a convergent approach. The key steps involve in this synthesis are Horner−Wadsworth−Emmons reaction, Sharpless asymmetric dihydroxylation, and acid-mediated ketalization to assemble the substituted THP ring, one-pot Sharpless dihydroxylation−S N 2-type cyclization, and Wittig homologation to construct the THF derivative.

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Au nified synthetic strategy has been developed for the total synthesis of the dendrodolide family,e mploying Jørgensen asymmetric epoxidation, Keck allylation, Brown allylation, Yamaguchi esterification,a nd ring-closing metathesis as key reactions. IntroductionIn recent years, many naturally occurring macrolides with different ring sizes have been isolated from fungal metabolites. These compounds play important roles in biochemical fields due to their variousb iological properties.[1] Many of them and their synthetic derivatives have been provent ob eb eneficial to human cells. Some 10 and 12-membered lactones and their derivatives, such as stagonolides, [2] recefeiolide, [3] cladospolides, [4] patulolides, [5] sporiolides, [6] and balticolid, [7] have anticancer,a ntibacterial, antiviral, antifungal, and cytotoxic activities.Recently,t he class of 12-membered macrolides named dendrodolides (Figure1)w ere isolated from Dendrodochium Sp.,afungus associated with the sea cucumber Holothurian nobilis Selenka, which wasc ollected from the South China Sea by Zhang and coworkers.[8] Thes tructures of these dendrodolides were elucidated by means of spectroscopic analysis and single crystal X-ray diffraction. The absolute configurations were assigned using the modified Mosher method, excitation-coupled circulard ichroism (ECCD), electronic solution and solid-state circular dichroism (ECD), supported by time dependent density functional theory (TDDFT) ECD calculations, andX -ray analysis. The dendrodolides have different levels of growth-inhibiting activity against SMMC-7721 and HCT116 cells in in vitro bioassays.Intramolecular ring-closing metathesis [9] is au seful tool for construction of macrolactones through CÀCb ondf ormation. It gives interesting results about the geometry of the newly formed doubleb ond and has been studied earlier.T he geometry of the double bond depends on the ring size and protecting groups present in substrates. As part of our ongoing research in exploring ring-closing metathesis reaction for macrolides synthesis, [10] herein we report the total synthesis of dendrodolides E, F, G, I, J, and L. Results and DiscussionAccording to our retrosynthetic analysis of dendrodolides as shown in Scheme 1, the macrolactones could be synthesized by ring-closing metathesis of the corresponding di and triolefinic esters 14-18.T hese di and triolefinic esters 14-18 could be prepared from the coupling of corresponding alcohols 19-23 with ak nown acid 24 [10a] under Yamaguchi esterification conditions. These two fragments could be derived from commerciallya vailable achiral starting materials trans-crotanaldehyde (25)a nd 1,3-propaned iol (26,Scheme 1). The synthesis of alcohol fragments 19 and 20 began with the enantioselective epoxidation of trans-crotanaldehyde (25) [11] with 2-[bis(3,5-bis(trifluoromethyl)phenyl)(trimethylsilyloxy)methyl]pyrrolidine as the chiral catalysttoa ffordt he chiral epoxide, which was followed by two-carbon Wittig olefination to form a,b-unsaturated epoxy ester 27 in ...