Oxabicyclo[3.2.1]octenes in Organic Synthesis:  Direct Ring Opening of Oxabicyclo[3.2.1] Ring Systems with Diisobutylaluminum Hydride and a Silyl Ketene AcetalSynthesis of the Chiral C(19)−C(26) and C(27)−C(32) Fragments of Scytophycin C

Abstract

[reaction: see text] An efficient strategy for transforming meso-oxabicyclo[3.2.1]octenone 1 into optically active intermediates for macrolide synthesis has been developed. The direct bridgehead opening of optically active oxabicyclo[3.2.1]octene derivative 2 with hydride or a silyl ketene acetal utilizing the highly polar medium lithium perchlorate in diethyl ether resulted in highly functionalized cycloheptenones, which were transformed into the C(19)-C(26) and C(27)-C(32) fragments of Scytophycin C.

Transition Metal-Catalyzed Enantioselective Ring-Opening Reactions of Oxabicyclic Alkenes

“…Similarly, ( R )- 20 was used to enantioselectively deprotonate 23 , which was trapped as the silyl enol ether 24 in 97% yield and 75% ee. Enol ether 24 is a key intermediate in the preparation of two fragments of scytophycin C …”

“…11 Similarly, (R)-20 was used to enantioselectively deprotonate 23, which was trapped as the silyl enol ether 24 in 97% yield and 75% ee. Enol ether 24 is a key intermediate in the preparation of two fragments of scytophycin C. 12 The third strategy, which until recently has received far less attention, employs a desymmetrization reaction as the ring-opening event. In this way, new stereocenters are established simultaneously as the meso symmetry is broken.…”

Perchloric Acid and Its Salts: Very Powerful Catalysts in Organic Chemistry

“…Oxabicyclo[3.2.1]octenes such as 209 can be opened at the bridgehead employing silyl ketene acetals or hydrides in 4.0−5.0 M LPDE to give rise to highly functionalized cycloheptadienes ( 211 , Scheme ) that can be further manipulated for use in natural product synthesis, for example, in the construction of the C(19)−C(27) fragment of rifamycin S or C(19)−C(26) and C(27)−C(32) fragments of scytophycin C, respectively. Moreover the reaction can be extended to other bicyclooctenes and silyl ketenes in 60−95% yield …”

Total Synthesis of Scytophycin C. 1. Stereoselective Syntheses of the C(1)−C(18) Segment and the C(19)−C(31) Segment

“…3 The potent biological properties of scytophycin C, its scarce availability from natural sources, and its close structural resemblance to the marine natural product swinholide A have stimulated considerable interest in its synthesis. [4][5][6][7][8][9][10] So far, an elegant total synthesis of scytophycin C has been achieved by Paterson by the judicious use of stereoselective aldol reactions. 4,5 We report Segment A containing the dihydropyran ring was efficiently and stereoselectively synthesized according to Scheme 2, which involves novel acyclic stereocontrol with double inversion of the configuration as the key step.…”

“…The scytophycins, a novel series of polyoxygenated 22-membered macrolides isolated from the terrestrial blue-green alga Scytonema pseudohofmanni , have demonstrated potent cytotoxicity against a variety of human carcinoma cell lines, as well as broad-spectrum antifungal activity. 1b,c, Among them, scytophycin C ( 1 ) isolated by Moore et al in 1986 1a has been demonstrated to exhibit significant activity against solid tumors in vitro . The potent biological properties of scytophycin C, its scarce availability from natural sources, and its close structural resemblance to the marine natural product swinholide A have stimulated considerable interest in its synthesis. − So far, an elegant total synthesis of scytophycin C has been achieved by Paterson by the judicious use of stereoselective aldol reactions. , We report herein the stereoselective total synthesis of scytophycin C ( 1 ) based on new acyclic stereocontrol. The structure of scytophycin C is characterized by a 22-membered macrolide containing a dihydropyran ring bearing two trans-substituted side chains and a unique polypropionate-derived structure having a terminal N -methyl- N -vinylformamide moiety in which 15 asymmetric centers are included in total.…”