Total Synthesis of Bistratamide D

Abstract

The total synthesis of the macrocyclic hexapeptide bistratamide D is reported. The synthetic strategy involved assembly of enantiomerically pure oxazole, thiazole, and oxazoline segments derived from amino acids. Macrocyclization of the hexapeptidic aminooxazoline-oxazole-thiazole carboxylic acid fragment was accomplished by activation with O-(7-azabenzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate (HATU).

The cyclization of peptides and depsipeptides

“…Having established the theme for synthesis, using the above examples, space only allows mention that the syntheses have also been recently published for cyclodidemnamide [184], lissoclinamides 4 and 5 [185], micrococcin P and P 1 [186,187], dolastatin I [188], mollamide [189], keranamide J [190], bistratamide D [191], 14,15 anhydropristinamycin II B (a virginiamycin) [192], lissoclinamide 7 [193] and raocyclamide [194]. Each one represents demanding exercises in the art of contemporary synthesis.…”

Total Synthesis of Diazonamide A

“…Prompted by this encouraging set of preliminary results, we then proceeded to apply the developed chemistry to the target molecule 2 as shown in Scheme . Having failed to successfully utilize the known oxazole ester derivative 15 16 in the intended coupling reaction, we resorted to its reduction (LiBH 4 ) and selective protection (60 % overall yield)17 to afford benzyl ether 6 as an alternative substrate for this process. Reaction of 6 with 2.0 equiv of n BuLi in THF at −78 °C resulted in the formation of dianion 16 which was treated with 1.1 equiv of isatin derivative 7 18 at −78 °C to afford, upon standard workup, tertiary alcohol 17 in 73 % yield.…”

6.13 Use of Carbonyl Derivatives for Heterocyclic Synthesis

“…15,16 In this reaction, α-halocarbonyl compounds are condensed with thioamides. In this reaction, the thioamide sulfur of 2 attacks the halogen carbon giving an intermediate imidothioate (3).…”