Stereoselective Synthesis of the C1–C9 and C11–C25 Fragments of Amphidinolides C, C2, C3, and F

Abstract

An efficient synthesis of the C1-C9 and the C11-C25 fragments of amphidinolides C, C2, C3, and F from a common intermediate is reported. The construction of the C1-C9 fragment involves an intramolecular hetero-Michael cyclization to form the 3,5-disubstituted trans-tetrahydrofuran moiety. The approach to prepare the C11-C25 fragment utilizes a highly stereoselective aerobic cobalt-catalyzed alkenol cyclization and a chelated Mukaiyama aldol reaction to form the C13-C14 bond and to concomitantly install the C13 hydroxyl group.

Total Synthesis of 12,13‐Dibenzyl‐banistenoside B and Analogs

“…The aldehyde intermediate 3 can be synthesized in gram scale from D-(+)-gluconic acid δ-lactone according to the known protocol in 5 steps with 70 % overall yield. [7][8][9][10] With aldehyde intermediate 3 in hands, we set for the first key reaction of the sequence PictetÀ Spengler cyclization under neutral conditions in consideration of the stability of the acetal with the freshly prepared 6-methoxytryptamine from 6methoxyindole (Scheme 2). [11][12][13] A diastereomeric mixture of 4 a and 4 b in the ratio of 1 : 1 and yield of 35 % was obtained, which were separated by column chromatography.…”

“…Our synthesis began with commercially available D‐(+)‐gluconic acid δ ‐lactone. The aldehyde intermediate 3 can be synthesized in gram scale from D‐(+)‐gluconic acid δ ‐lactone according to the known protocol in 5 steps with 70 % overall yield [7–10] . With aldehyde intermediate 3 in hands, we set for the first key reaction of the sequence Pictet−Spengler cyclization under neutral conditions in consideration of the stability of the acetal with the freshly prepared 6‐methoxytryptamine from 6‐methoxyindole (Scheme 2).…”

Total Synthesis of Meayamycin and O-Acyl Analogues

“…Central to the synthesis of 15 was use of the known starting material 9 , the BocNH- l -Thr derived variant of Garner’s aldehyde, available in three steps from BocNH- l -Thr (1 equiv of MeONHMe, 1.2 equiv of EDCI, 1.2 equiv of HOBt, 2 equiv of ( i Pr 2 )­NEt, CH 2 Cl 2 , 23 °C, 22 h; 0.2 equiv of PPTS, 10 equiv of MeC­(OMe) 2 Me, THF, reflux, 18 h, 85–88% for two steps), including the reported DIBAL-H reduction of the Weinreb amide (2 equiv DIBAL-H, CH 2 Cl 2 , −78 °C, 3 h) . A Z -selective modified Wadsworth–Horner–Emmons reaction of 10 with aldehyde 9 provided the α,β-unsaturated ester 11 (86% for two steps, 4.6:1 Z / E ) where preferential generation of the Z -isomer facilitates but may not be required for an ensuing lactonization. Acid-catalyzed N , O -ketal cleavage effected with 10-camphorsulfonic acid (CSA) and in situ lactonization (0.04 equiv of CSA, MeOH, 23 °C, 74%) provided 12 in a single step.…”

Retrosynthetic Analysis of α-Alkenyl-β-Diketones: Regio- and Stereoselective Two-Step Synthesis of Highly Arylated Representatives from Acetylenes, Ketones, and Acyl Chlorides

“…Dichloromethane was distilled over phosphorus pentoxide and stored over 4 Å MS in order to remove any water. Magnesium bromide ethyl etherate was prepared from magnesium turnings and 1,2-dibromoethane in diethyl ether …”