An alternative stereoselective total synthesis of Verbalactone

Abstract

A simple and efficient synthesis of Verbalactone has been accomplished from inexpensive and commercially available starting material, hexanal. This concise synthesis utilizes stereoselective reduction of β-hydroxyketone using catecholborane, regioselective opening of epoxide and Yamaguchi reaction for the construction of the macrolactone.

Total synthesis of both enantiomers of the biosurfactant aureosurfactin via bidirectional synthesis with a chiral Horner–Wittig building block

“…Due to the uncertainty with regard to the absolute configuration of the natural surfactant, we decided to develop a de novo synthesis for both enantiomers of aureosurfactin ( 1 ). We point out that several syntheses of (3 R ,5 R )-3,5-dihydroxydecanoic acid have been described in connection with the synthetic entries toward verbalactone, 17 The synthesis of methyl (3 S ,5 S )-3,5-dihydroxydecanoate has been reported by Mineeva. 18 For the construction of (3 S ,5 S ,3′ S ,5′ S )- and (3 R ,5 R ,3′ R ,5′R)-aureosurfactin ( 1 ), respectively, we envisioned the protected 3,5-dihydroxydecanoic acids 2a und 2b as key intermediates where the 5-OH bears a triethylsilyl-(TES) group that can be selectively removed over the tert -butyldimethylsilyl-(TBS) group attached at the 3-OH, thus making the coupling of both fragments via ester formation possible.…”

Radical Simplification of Complex Molecule Retrosynthesis Enabled by Electrocatalytic Cross-Coupling of α-Substituted Carboxylic Acids

“…In contrast a cis-selective dDCC using the common diol unit 6-RAE completed the total synthesis in merely 3 steps (67% ideality) by quickly assembling the carbon skeleton followed by lactonization. Verbalactone (42), possessing unique activity against various Gram-positive and Gram-negative bacteria, 23 is an interesting case for analysis as it has been prepared at least 14 different ways ranging from 7-22 step-count (57% ideality for the shortest route). Although a macrolactonization approach to unite the two symmetrical fragment is common, accessing the key fragment requires multiple concession steps regardless of the strategy employed such as a combination of dithiane chemistry and chiral epoxide opening 23,24 or asymmetric allylation.…”

“…Verbalactone (42), possessing unique activity against various Gram-positive and Gram-negative bacteria, 23 is an interesting case for analysis as it has been prepared at least 14 different ways ranging from 7-22 step-count (57% ideality for the shortest route). Although a macrolactonization approach to unite the two symmetrical fragment is common, accessing the key fragment requires multiple concession steps regardless of the strategy employed such as a combination of dithiane chemistry and chiral epoxide opening 23,24 or asymmetric allylation. 25 Again, the radical approach described herein employs a cis-selective dDCC on 6-RAE with hexanoic acid RAE followed by deprotection of the acetonide and tert-butyl ester, delivering the key symmetrical unit in 2 steps.…”

Biochemical Symmetrization/ Desymmetrization of Organic Compounds: Dendrimeric Relationship with Molecular Formulas

“…a biennial plant of the genus Verbascum that belongs to the family Scrophulariaceae. These compounds were also prepared by chemical synthesis [56][57][58].…”