Total Synthesis of Meayamycin and O-Acyl Analogues

Abstract

A short, scalable total synthesis of meayamycin is described by an approach that entails a longest linear sequence of 12 steps (22 steps overall) from commercially available chiral pool materials (ethyl L-lactate, BocNH-Thr-OH, and D-ribose) and introduces the most straightforward preparation of the right-hand subunit detailed to date. The use of the approach in the divergent synthesis of a representative series of O-acyl analogues is exemplified.

Advancements in Enacyloxins Total Synthesis: Access to the Chlorinated Polyunsaturated Chain Peculiar to this Promising Family of Antibiotics

“…This reaction obeyed the Baldwin rules 37 as only tetrahydropyranone formed (IR C�O absorption at 1716 cm −1 ). 38 This type of transformation has been previously reported only with enolboranes. 39 Ultimately (entry 5), we were delighted to see that BF 3 •OEt 2 with TBS enolsilane of ketone 43b gave aldol product 44b in 63% yield, when the reaction and quench were conducted at −80 °C.…”

Improved Synthesis of the Amine Fragment of FR901464 and Thailanstatins through the Development of a Convenient N-Detosylation Method

“…Small molecules that bind the human spliceosome proteins have garnered interest in recent years. − FR901464 − and closely related small molecules represent a class of natural products that bind and modulate the function of the human splicing factor 3B (SF3B) complex. Total syntheses of FR901464 and similar natural products (Figure ) have been reported by the Jacobsen, , Kitahara, , Ghosh, − Webb, − Arisawa, , Nicolaou, − and Boger groups and by us. − We began synthesizing the A ring fragment from the l -threonine derivative, , and the Boger group improved the efficiency of the synthesis by carefully analyzing side reactions. Thus, this synthetic route appears to remain useful for the medicinal chemistry campaign.…”

Spliceostatins and Derivatives: Chemical Syntheses and Biological Properties of Potent Splicing Inhibitors

“…Boger and co-workers reported an efficient synthesis for meayamycin A ( 90 ) and its O -acyl analogues in 2020 . A short and scalable synthesis was developed utilizing the chiral pool for starting materials, in which all chirality was introduced or controlled by the chirality present in the starting materials.…”

“…Known Boc-protected Garner’s aldehyde 43 was converted to amine 226 using a similar protocol reported by Koide and co-workers with only slight modifications. ,, Amine 226 was coupled with acid 16 to furnish amide 84 , whereas coupling with 42 gave amide 227 . Interestingly, it was found that utilizing acid 42 allowed for higher overall yields due to increased alcohol stability and avoidance of Z to E olefin isomerization …”

“…Interestingly, it was found that utilizing acid 42 allowed for higher overall yields due to increased alcohol stability and avoidance of Z to E olefin isomerization. 131 Acid 16 was independently synthesized in a similar fashion to that reported by Ghosh, 48 and 42 was synthesized with only slight modifications to the route reported by Kitahara. 42,43 Alkene 227 could be converted to the acetylated derivative via TBDPS deprotection and acetylation.…”