No abstract

The stereoselective total synthesis of cytotoxic marine macrolide callyspongiolide has been reported. The 14-membered macrolactone ring along with Z -olefin in the molecule was constructed via an intramolecular Horner–Wadsworth–Emmons olefination in a Z -selective fashion. The other E -olefinic moiety as well as the C9 stereocenter was introduced via stereoselective addition of the methyl group in an S N 2′ fashion. The C5 stereocenter was installed via Sakurai allylation, whereas the C7 center was fixed by Jacobsen hydrolytic kinetic resolution. The C12 methyl and C13 hydroxy centers were fixed via Macmillan coupling reaction. The macrolactone core with a vinyl iodide side chain was coupled with the known alkyne fragment to complete the synthesis.

A concise synthetic strategy has been developed for the synthesis of the macrolactone core 2 of a unique polyketide callyspongiolide 1. The key features of the strategy included an Evan's asymmetric alkylation, diastereoselective Michael type alkylation, Brown's asymmetric allylation reaction, an allylic alkylation of an activated Z-allylic alcohol and an intramolecular Z-selective intramolecular H-W-E olefination.

SummaryA practical, mild and efficient protocol for the Pictet–Spengler reaction catalyzed by cyanuric chloride (trichloro-1,3,5-triazine, TCT) is described. The 6-endo cyclization of tryptophan/tryptamine and modified Pictet–Spengler substrates with both electron-withdrawing and electron-donating aldehydes was carried out by using a catalytic amount of TCT (10 mol %) in DMSO under a nitrogen atmosphere. TCT catalyzed the Pictet–Spengler reaction involving electron-donating aldehydes in excellent yield. Thus, it has a distinct advantage over the existing methodologies where electron-donating aldehydes failed to undergo 6-endo cyclization. Our methodology provided broad substrate scope and diversity. This is indeed the first report of the use of TCT as a catalyst for the Pictet–Spengler reaction.