Asymmetric Total Synthesis of (+)‐Neooxazolomycin Using a Chirality‐Transfer Strategy

Abstract

The total synthesis of (+ +)-neooxazolomycin was achieved from the amino-acid d-serine.T he efficiency of this approach is derived from the use of principles of memory of chirality and dynamic kinetic resolution in the intramolecular aldol reaction of as erine derivative to build the densely functionalizedl actam framework and to install three contiguous stereocenters.T he key intermediate was readily elaborated to the target natural product.Supportinginformation and the ORCID identification number(s) for the author(s) of this article can be found under: https://doi.

The oxazolomycin family: a review of current knowledge

“…These fragments and their analogues are crucial intermediates for total syntheses of all members of oxazolomycin family reported to date. 12,13,[15][16][17] The le-hand fragment represents one of two different structural arrangements. The most common framework is the oxazole-triene-amide 18 also known as inthomycin derivative.…”

“…2) with (4Z,6Z,8E)-congurated triene is present in the structures of oxazolomycin A, oxazolomycin A2, neooxazolomycin, 16-methyloxazolomycin, curromycin A, curromycin B, KSM-2690 B and in the both segments of bisoxazolomycin. Inthomycin B (17) which possesses (4Z,6E,8E)-congurated triene is present in the structures of oxazolomycin C and KSM-2690 C. Finally, inthomycin C (18) with (4E,6E,8E)-congurated triene moiety represents le-hand fragment of oxazolomycin B. The second structural framework for le-hand fragment is tetraene-nitro-hydroxy-amide which is typical for all lajollamycins including lajollamycin, lajollamycin B, lajollamycin C and lajollamcin D.…”

“…Kim et al reported in 2019 a total synthesis of neooxazolomycin (2) using a chirality-transfer strategy. 17 The six stereocenters of right-hand fragment were derived from D-serine by a series of chirality-transfer processes. Intramolecular aldol reaction was carried out with EtONa in EtOH and desired aldol product 140 was obtained with perfect enantioselectivity (>99% ee) in 61% yield.…”

“…The congurations of the three contiguous stereocenters were unambiguously conrmed by XRD analysis. 17 To introduce the exocyclic carbon chain, the benzyl protection group was removed under conditions of catalytic hydrogenation with H 2 , Pd/C in MeOH/AcOH (2 : 1) to produce primary alcohol 141 in 97% yield. Following oxidation with TEMPO, TCCA in CH 2 Cl 2 gave aldehyde 142 in 84% yield.…”

“…The stereochemistry of reduced product 145 was conrmed by XRD analysis. 17 The lactone ring opening was performed with N,O-dimethylhydroxylamine hydrochloride and i-PrMgCl in THF to give compound 146 in 92% yield. Inversion of hydroxyl group on C4 was achieved by sequential oxidation with NMO, TPAP in CH 2 Cl 2 to The protection was carried out with TMSCl and HMDS in pyridine and gave compound 149 in 94% yield without undesired lactonization.…”