Convergent Stereoselective Synthesis of the C16–C37 Subunit of Sorangicin A

Abstract

A convergent stereoselective route to the C16–C37 fragment of sorangicin A is disclosed using an α-chloro sulfide for C–C bond formation. The key intermediate, an α,β-unsaturated ketone, is revealed by a [2,3] sigmatropic rearrangement of a propargylic sulfoxide. Three disparate approaches are detailed to create the C25 carbinol stereocenter. The cis-2,6-disubstitution of the THP ring is secured by ionic hydrogenation. A cross-metathesis reaction and Julia–Kocienski olefination furnish the C16–C37 fragment of sorangicin A.

Recent Applications and Trends in the Julia‐Kocienski Olefination

“…the subunit C16−C37 of Sorangicin A was stereoselectively synthesised in a convergent manner via Julia‐Kocienski olefination, which played a vital role(Scheme 5). [17] This compound was first isolated by Hofle and Reichenbach from Sorangium Cellulosum [18] and it shows antibacterial activity against gram negative and gram positive bacteria via in vivo RNA polymerase inhibition [19] . The requisite sulfone 40 reacts with aldehyde 39 under Julia‐Kocienski conditions to afford the required E ‐olefin 41 furnished by the C16−C37 segment of Sorangicin A 42 .…”

“…As reported by Raghavan et al the subunit C16À C37 of Sorangicin A was stereoselectively synthesised in a convergent manner via Julia-Kocienski olefination, which played a vital role(Scheme 5). [17] This compound was first isolated by Hofle…”

Metathesis Reactions in Natural Product Fragments and Total Syntheses

“…Raghavan's group demarcated the convergent stereoselective synthesis of sorangicin A C16–C37 fragment 933 (Scheme 146). Sorangicin A is a characterized structurally intricate macrolide, isolated from myxobacteria Sorangium cellulosum and possess strong antibiotic activity [327a] . In this beautiful strategy, the CM was one of the crucial transformations employed to combine two building blocks.…”

Diastereodivergent Synthesis of 2-Ene-1,4-hydroxy Sulfides from 2-Sulfinyl Dienes via Tandem Sulfa-Michael/Sulfoxide-Sulfenate Rearrangement

“…Within this field, thiol or thiolate additions to substituted alkenyl sulfoxides are relatively rare and unselective in some cases . In recent years we have been involved in the application of readily available 1-sulfinyl dienes A and 2-sulfinyl dienes C (X = O, NTs, NR′; Y = O, NR′; Scheme ) in stereoselective synthesis, including the conjugate addition of amines and alkoxides (R 3 YH, RXH) to produce allylic sulfoxide intermediates that underwent a [2,3]-sigmatropic rearrangement, ultimately leading to 1,4-diol or 1,4-aminoalcohol derivatives B in a cascade process, with good yields and stereoselectivities . These results prompted us to examine the conjugate addition of thiolates to 2-sulfinyl dienes D , readily available from iodides or stannanes 1 (Scheme ), that could afford allylic sulfoxides E , and ultimately lead to allylic sulfides F .…”

“…These results prompted us to examine the conjugate addition of thiolates to 2-sulfinyl dienes D , readily available from iodides or stannanes 1 (Scheme ), that could afford allylic sulfoxides E , and ultimately lead to allylic sulfides F . The possibility of benefiting from the useful reactivity of enantiopure allylic sulfides F in highly stereocontrolled processes entailing sigmatropic rearrangements was an additional point of interest to embark on this study. ,− …”