A total synthesis of (.+-.)-tirandamycin B

Abstract

The total synthesis of the dienoyl tetramic acid antibiotic (i)-tirandamycin B is described. The key transformations of the strategy include (1) cyclization of pyranone 14 with fluorosilicic acid to provide the 2,6-dioxabicyclo[3.3.1 Jnonane system of the natural product, (2) reductive removal of the benzyl ether from enone 15, and (3) attachment of the tetramic acid moiety by using the Schlessinger phosphonate protocol. Protection of the primary hydroxyl function of tirandamycin B as the triisopropylsilyl (TIPS) ether was crucial to the success of the strategy. Tirandamycin B (l)1 is a member of the 3-dienoyl tetramic acid family of antibiotics. This family includes several structurally related substances such as tirandamycin A (2),2 streptolydigin (3),3 nocamycin,4 and Bu-2313 A and B.5 These substances display a diversity of biological activities. For example, tirandamycin B has been shown to possess antimicrobial activity by interfering with the function of bacterial DNA-directed RNA

A simple and efficient method for the preparation of 5-hydroxy-3-acyltetramic acids

“…Several attempts to remove the benzyl group under various catalytic hydrogenation conditions failed entirely. Cleavage of the DMB group with TFA [ 16 ] was also tried, but brought no success and extensive formation of polymerization products of the corresponding iminium ion was observed. Oxidative cleavage of the DMB group with CAN [ 17 ] produced no product either.…”

Synthesis and Biological Evaluation of the Novel Growth Inhibitor Streptol Glucoside, Isolated from an Obligate Plant Symbiont

“…Conventional methods using Birch conditions [25] (Na/NH3 at -78°C) did not result in any product. The milder conditions of lithium di-tert-butylbiphenyl (LiDBB) [26] at -78°C provided A-79197-2 (4) but in a rather low 24% yield over 2 steps. A more successful debenzylation was achieved using lithium naphthalenide (LiNp), [27] which prevented the cleavage of the allylic alcohol and gave the product 4 in reasonable yield (53% over 2 steps).…”

Recent Advances in the Total Synthesis of Tetramic Acid-Containing Natural Products

“…Obviously, the racemic tetramic acid fragment 33 could be easily accessed by subjecting phosphonate 31 to glycine methyl ester to provide the amide 32 that further proceeded with a typical Lacey-Dieckmann cyclization and a DMB protection (Schlessinger et al had prepared similar tetramic acid core via the same method in his synthesis of tirandamycin A; see [48]) [49]. In contrast, the bicyclic ketal fragment 36 asks for precautious design to achieve the desired stereochemistry presented in tirandamycin C [25,48,[50][51][52][53][54][55][56]. The starting homoallylic alcohol 34, prepared from the mismatched double asymmetric stannylcrotylboration of an aldehyde, was treated with excess MeLi at low temperature to trigger the formation of the lactol intermediate C.…”