Total synthesis of (+/-)-phloeodictine A1, a novel biomimetic route to the 3-acyl-5-hydroxy-3-pyrrolin-2-one and 3-acyl-3,4-epoxy-5-hydroxypyrrolidin-2-one ring systems and syntheses of ficuseptine, juliprosine, and juliprosopine

The antitumor antibiotic phloeodictine A1 has been synthesized by a convergent seven-step route in 8% overall yield. The key step was the Eguchi aza-Wittig reaction of the azide to give furan protected amidine followed by a retro Diels-Alder reaction to liberate amidine. Addition of 11-dodecenylmagnesium bromide to the amidine gave the C-6 alkylated amidine of the phloeodictine A1 core, alkylation with the bis Boc-protected guanidino iodide and deprotection completed the first synthesis of phloeodictine A1.; Modified Moffat oxidation of primary alcohols of phenylalaninol or prolinol afforded aldehydes that underwent intramolecular aldol reactions on treatment with a NaOH solution to yield 4-pyrrolin-2-ones. Oxidation with DMDO at -40°C provided 3-acyl-5-hydroxy-3-pyrrolin-2-ones with the ring system of oteromycin, UCS 1025A, and related natural products. Further oxidation of the 3-acyl-5-hydroxy-3-pyrrolin-2-one yielded 3-acy1-3,4-epoxy-5-hydroxy-pyrrolidin-2-one with the ring system of fusarin C and epolactaene. Dehydration of 3-acyl-5-hydroxy-3-pyrrolin-2-one afforded the dime compound with the talaroconvolutin A ring system.; Biomimetic intramolecular Chichibabin pyridine syntheses using two molecules of an aldehyde and 4-aminobutanal dimethyl acetal proceed efficiently in AcOH at 95°C to give 2,3-dihydro-1H-indolizinium salts. Reaction occurs at 25°C if 1-pyrroline is used instead of 4-aminobutanal dimethyl acetal. This reaction has been used for a one step synthesis of ficuseptine and the first syntheses of juliprosine and juliprosopine, which is now assigned as the trans stereoisomer.