Convergent Synthesis of the C18-C30 Fragment of Amphidinol 3

Abstract

The C18-C30 fragment of amphidinol 3 has been synthesized in a convergent fashion by employing two asymmetric Sharpless dihydroxylations, a Julia-Kocienski olefination and a Wittig reaction as the key steps.

Integrated approaches to the configurational assignment of marine natural products

“…It was uncertain how the misassignment was made, but an HPLC peak corresponding to the protected ester 24 may have contaminanted the degradation product. Amphidinol 3 ( 19 ) has been the subject of intense synthetic efforts by research groups led by Cossy, lxvii Rychnovsky, lxviii Roush, lxix Paquette, lxx Oishi, lxxi Crimmins, lxxii and Marko. lxxiii …”

Synthesis and Structure Revision of the C43–C67 Part of Amphidinol 3

“…Amphidinol 3 (AM3, 1 , Figure ), produced by the dinoflagellate Amphidinium klebsii , elicits high antifungal efficacy with submicromolar IC 50 values despite its relatively potent hemolytic activity (EC 50 = 0.25 μM). , These biological activities can be accounted for by formation of ion-permeable pores in a sterol dependent manner . The striking structural features of AM3 have attracted considerable attention from the synthetic community. − Because of the limited availability of the natural product, and the presence of a number of stereogenic centers on the long acyclic carbon chain, it has been difficult to determine the molecular structure of AM3. Although the stereochemistry of AM3 was determined in 1999 based on the J -based configuration analysis (JBCA) method, modified Mosher method, and degradation of the natural product via oxidative cleavage, the absolute configuration at C2 was later revised to be R by comparing synthetic specimens with a fragment of AM3 by GC–MS .…”

Isolation, structural determination and synthetic approaches toward amphidinol 3

“…This compound was then converted to the C26-C42 fragment 106 in four steps involving a Claisen rearrangement 100 of a 1,5-diene to introduce the C30-C31 double bond (Scheme 34). 101,105,106,112,115,119,123,125 These three groups are working together on the synthesis of AM3. The rst strategy envisaged to construct AM3 was disclosed by Cossy and Bouzbouz and consisted of the construction of the C30-C31 and the C52-C53 bonds using olenations.…”

“…). 112 As the formation of the C17-C18 bond was planned in the synthesis of the C1-C30 fragment, fragment C18-C30 was prepared. The synthesis of this fragment (compound 135) has been envisaged from 129 and 132 by using a Wittig reaction to merge these two compounds and by applying an enantioselective Sharpless dihydroxylation to control the absolute conguration at C20 and C21 (Scheme 38).…”