Total Synthesis of Lajollamycin B

Abstract

The first total synthesis of lajollamycin B, as tructurally novel nitro-tetraene spiro-b-lactone/g-lactonea ntibiotic, is described. The convergent synthesis involves the construction of the C8'-C11' nitrodienylstannane and its coupling with the segment prepared from the C1'-C7' w-iodo-heptadienoic acid and the right-hand heterocyclic fragment, which has been utilized for our previouss yntheses of oxazo-lomycinA.T he revisiono ft he geometry of the terminal D 10',11' -double bond from E to Z is also described for the structure of natural lajollamycin B.

The oxazolomycin family: a review of current knowledge

“…9 However, in 2019 Hatakeyama et al reported rst total synthesis of lajollamycin B and its C10 0 geometric isomer. 15 Surprisingly, a spectroscopic comparison with data for 11 reported by Oh et al 9 found to be identical with unexpected isomer. Thus, Hatakeyama et al carefully reinvestigated Oh's 2D NMR spectroscopic data of 11 and unambiguously assigned NOESY spectra to both prepared isomers.…”

“…According to these ndings Hatakeyama et al revised the initially assigned geometry of lajollamycin B from (10 0 E)-to (10 0 Z)-congurated double bond. 15 The last two members of oxazolomycin family were isolated, characterized and reported in 2017 by Koomsiri et al 10 Both structures were elucidated using HR-ESI-MS, UV and IR spectra, optical rotation, 1D and 2D NMR spectroscopy. Structure of oxazolomycin A2 (14) indicated close similarity to oxazolomycin A (1), but difference in chemical shis of the oxymethylene H 2 -16 was observed.…”

“…10 Moreover, oxazolomycin A2 has been synthetized as an intermediate in total synthesis of 1 reported by Hatakeyama et al in 2011, however crude 14 was directly used to further reaction without isolation. 12 Spectral data of bisoxazolomycin (15) suggested that structure is an asymmetric dimer of 1 consisting of N-methyl-g-lactam segments I and II. 10 Both segments were conrmed by the 1 H- 13 C long-range correlations.…”

“…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.…”

“…10 3.2.3 Antifungal activity. Koomsiri et al investigated the antifungal activity of oxazolomycin A (1), A2 (14) and bisoxazolomycin (15) against Aspergillus niger ATCC 6275, Candida albicans ATCC 64548, Mucor racemosus IFO 4581 and Saccharomyces cerevisiae ATCC 9763 using the paper disc method (disc diameter ¼ 6 mm, applied concentrations: 1, 3, 10 and 30 mg per disc). 10 However, no antifungal activity was observed.…”