Total Synthesis of Viridiofungins A and B

Abstract

The total synthesis of viridiofungins A (1) and B (2) via β-lactone 3 in 13 steps is reported. Key steps included an HF-mediated rearrangement of cyclobutene diester 9 to form a bicyclic lactone 6, an olefin cross metathesis between disubstituted alkene 3 and alkene 4 in which isomerization was suppressed, and a novel β-lactone ring opening to form the amide. Deprotection then gave either viridiofungin A (1) or B (2) in high yield.

Diastereoselective and Enantioselective Synthesis of α-p-Methoxyphenoxy-β-Lactones: Dependence on the Stereoelectronic Properties of the β-Hydroxy-α-p-Methoxyphenoxycarboxylic Acid Precursors

“…In addition to their occurrence in natural products, β-lactones have proven to be effective tools in the synthesis in a variety of natural products including brefeldin, muqubilin, negombatoperoxides, , viridiofungins, vinigrol, and zaragozic acid as key synthetic intermediates (Figure ). These studies have served to increase the interest in the development of methods for synthesizing β-lactone intermediates.…”

Synthesis of More Highly Oxidized Alkyl Citrates via Direct Regio- and Stereoselective Oxidation

“…A starting point for this would be bicyclic lactone 9 , which is readily available in four steps and high diastereoselectivity from ( S )-γ-lactone 10 (Scheme ). Compound 9 has been previously utilized by us for the total synthesis of the corrected structure for citrafungin A and viridiofungins A and B . Direct selective oxidation at C4 and C2 of labile lactone 9 would be challenging, so it was envisaged that the formation of the C4 tertiary alcohol prior to the secondary alcohol at C2 could be achieved from the derived intermediates.…”

“…Conversion of bicyclic lactone 9 to acid 20 followed our previously reported procedure (Scheme ). Acid 20 was converted into tert -butyl ester 11 upon treatment with O - tert -butyl- N,N -diisopropylisourea. Olefin cross metathesis mediated by a Grubbs–Hoveyda second-generation catalyst in the presence of 2,6-dichloro-1,4-benzoquinone to thwart alkene isomerization , followed by alkene reduction and concomitant benzyl ether hydrogenolysis afforded extended diol 21 in good yield over two steps.…”

“… Acid 20 was converted into tert -butyl ester 11 upon treatment with O - tert -butyl- N,N -diisopropylisourea. Olefin cross metathesis mediated by a Grubbs–Hoveyda second-generation catalyst in the presence of 2,6-dichloro-1,4-benzoquinone to thwart alkene isomerization , followed by alkene reduction and concomitant benzyl ether hydrogenolysis afforded extended diol 21 in good yield over two steps. DMP oxidation of the primary alcohol and treatment of the crude aldehyde with the anion derived from phosphonate 22 under modified conditions , afforded the desired styrene 23 with excellent stereochemical control (>95:5 E : Z ratio).…”