Abstract:The enantiodivergent formal syntheses of both enantiomers of aspercyclide C is accomplished. Starting from L-(+)-tartaric acid, the key protected allylic alcohol, (3R,4R)-4-(methoxymethoxy)non-1-en-3-ol is prepared, and is then elaborated into both enantiomers of 3-[(4-methoxybenzyl)oxy]non-1-en-4-ol via Mitsunobu inversion. Esterification with a known biaryl acid, followed by ring-closing metathesis and deprotection completes the syntheses.
“…The diols were employed in the total synthesis of several natural products including macrolactones such as cladospolides, palmerolide A, microcarpalide and aspercyclide C (Scheme 5). [23–30] …”
“Chiral pool” compounds possessing well defined stereocenters and suitable functionality serve as excellent building blocks for the synthesis of natural products and therapeutically important compounds. Tartaric acid is a C2‐symmetric molecule available in both enantiomeric forms. It was extensively utilized in the synthesis of privileged chiral ligands/catalysts such as TADDOLs, and as a start point in the synthesis of plethora of compounds. The advent of several new C−C bond forming reactions offers opportunity for the development of novel synthetic strategies based on chiral pool compounds. We found that the desymmetrization of the bis‐dimethyl amide/Weinreb amide derived from tartaric acid can be accomplished by controlled addition of Grignard /organolithium reagents leading to the mono keto amides, the reduction of which affords the γ‐hydroxy amides. This account describes our research efforts of more than a decade on the synthesis and application of diverse γ‐hydroxy amides derived from tartaric acid in the total synthesis of structurally simple to complex bio‐active natural products.
“…The diols were employed in the total synthesis of several natural products including macrolactones such as cladospolides, palmerolide A, microcarpalide and aspercyclide C (Scheme 5). [23–30] …”
“Chiral pool” compounds possessing well defined stereocenters and suitable functionality serve as excellent building blocks for the synthesis of natural products and therapeutically important compounds. Tartaric acid is a C2‐symmetric molecule available in both enantiomeric forms. It was extensively utilized in the synthesis of privileged chiral ligands/catalysts such as TADDOLs, and as a start point in the synthesis of plethora of compounds. The advent of several new C−C bond forming reactions offers opportunity for the development of novel synthetic strategies based on chiral pool compounds. We found that the desymmetrization of the bis‐dimethyl amide/Weinreb amide derived from tartaric acid can be accomplished by controlled addition of Grignard /organolithium reagents leading to the mono keto amides, the reduction of which affords the γ‐hydroxy amides. This account describes our research efforts of more than a decade on the synthesis and application of diverse γ‐hydroxy amides derived from tartaric acid in the total synthesis of structurally simple to complex bio‐active natural products.
“…The Yamaguchi esterification of acid fragment 12 and alkenol derivative 11a could also lead to the required bis-olefin derivative 10. 31 The bis-olefin derivative 10 could then be converted into the target compound cytospolide D 4 by the Grubbs RCM and deprotection of both protecting group following the standard organic transformations. Ramana et al reported the synthesis of Cytospolide E 5 with similar fargments with different stereochemistry.…”
Section: Synthesis Of the C1-c4 Fragment (12)mentioning
“…They exhibit moderate activity in IgE receptor binding related to allergic disorders. Prasad and co-workers 35 described enantiodivergent routes to aspercyclide C enantiomers from L-tartaric acid. The key common intermediate is the protected allylic alcohol (3R,4R)-4-(methoxymethoxy)non-1-en-3-ol, which after protection as PMB ether and MOM deprotection, the configuration of the alcohol was inverted under Mitsunobu conditions (Scheme 24).…”
Section: Scheme 23 Enantiodivergent Routes To (S)-and (R)-zaeralanesmentioning
Enantio- and diastereodivergent routes to marine-origin natural products, lactones, other natural products, heterocycles and unnatural compounds are considered.
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