Synthesis of an Oxazoline Analogue of Apratoxin A

Abstract

[structure: see text] Michael addition of Me(2)Cu(CN)Li(2) to alpha,beta-unsaturated lactone 7 derived from beta-hydroxyl ketone 5 provides lactone 8, which is converted to alcohol 11 using Oppolzer's methodology as the key step. Connection of 11 with the l-proline moiety and subsequent installation of an oxazoline ring affords 16, which is coupled with tripeptide 21; subsequent macrocyclization then furnishes 4, an oxazoline analogue of apratoxin A.

Synthesis of the Biologically Active Natural Product Cyclodepsipeptides Apratoxin A and Its Analogues

“…Wipf and Uto elegantly demonstrated that the oxazoline moiety was ringopened to the corresponding thioamide on a cyclic peptide by treatment with H 2 S, and then dehydrative cyclization using N,N-dimethylaminosulfur trifluoride (DAST) led to the total synthesis of the thiazoline-containing cyclic peptide trunkamide A. 13) We initially synthesized the oxazoline analogue of apratoxin A (16) 7,14,15) and attempted to convert the oxazoline moiety to a thiazoline ring. triazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (HATU)/N,N-diisopropylethylamine (DIEA)), gave undesired azlactone 10 in 49% yield, along with the desired tetrapeptide 9 in only 21% yield.…”

Filamentous tropical marine cyanobacteria: a rich source of natural products for anticancer drug discovery

“…Due to the structural novelty, coupled with the exceptional biological activity of apratoxin A, several synthetic research groups carried out total synthesis of 67 and its analogues (73-76) (Fig. 8) for the purpose of SAR studies (Chen and Forsyth 2003a;b;Chen and Forsyth 2004;Zou et al 2003;Doi et al, 2006;Ma et al 2006;Numajiri et al 2009;Gilles et al 2009). An oxazoline analogue of apratoxin A, oxapratoxin A (73), was found to be slightly lower in potency against HeLa cells when compared with apratoxin A (Table 2; Ma et al 2006).…”

Total synthesis of the marine cyanobacterial cyclodepsipeptide apratoxin A

“…Chemical synthesis may complement this potential by offering an expedient route to structurally diversify the apratoxin chemotype. Accordingly, a few studies related to the chemical synthesis of the apratoxins have been published (19,20), including the synthesis an oxazoline-containing analog (21). A complete total synthesis can also address the immediate apratoxin supply limitation and corroborate the assigned structures of the natural products.…”