Stereoselective Construction of C 2 -Symmetric Adjacent Bis-α,α′- cis -Disubstituted THF Skeleton via Double Intramolecular Amide Enolate Alkylation: Total Syntheses of (+)-Membranacin and (+)-Squamocin-N

Srinivas Batthula; Sudharshan Reddy Sanapalli; Mallesham Samala; Rapelli Chandrashekhar; Minjung Kwak; Nageswarao Yalavarthi; Seok Ho Kim; Deukjoon Kim; JongKook Lee

doi:10.1021/acs.orglett.5c05114

Stereoselective Construction of C 2 -Symmetric Adjacent Bis-α,α′- cis -Disubstituted THF Skeleton via Double Intramolecular Amide Enolate Alkylation: Total Syntheses of (+)-Membranacin and (+)-Squamocin-N

Organic Letters 2026

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Authors: Srinivas Batthula, Sudharshan Reddy Sanapalli, Mallesham Samala, Rapelli Chandrashekhar, Minjung Kwak, Nageswarao Yalavarthi, Seok Ho Kim, Deukjoon Kim, JongKook Lee

DOI: 10.1021/acs.orglett.5c05114

Cited by: 0

References: 30

Abstract

Described herein is the highly stereoselective and concise first asymmetric total synthesis of (+)-squamocin-N ( 1b ) bearing a C15–C24 adjacent bis-tetrahydrofuran (THF) backbone with threo/cis/threo/cis / threo stereochemistry. This approach features construction of C 2 -symmetric adjacent cis/threo/cis bis-THF core 5 via a novel double intramolecular amide enolate alkylation (IAEA) protocol, reductive desymmetrization of C 2 -symmetric bis-THF 5, and chelation-controlled nucleophilic addition (CCNA) as the key steps. In addition, (+)-membranacin ( 1a ), the C24 epimer of 1b, was synthesized via Mitsunobu inversion.

Fields of Study & Subjects

Traditional and Medicinal Uses of Annonaceae Synthetic Organic Chemistry Methods Chemical synthesis and alkaloids

Publication details

Journal / source: Organic Letters
Volume: 28
Issue: 2
Pages: 860–865
Publication date: 2 January 2026
Language: EN

References 30