First Total Synthesis of the Novel Brominated Polyacetylenic Diol (+)–Diplyne A and (+)–Diplyne C

by Gibeau, Craig R.

This thesis describes the methodology and experimental work in the total synthesis of two novel brominated polyacetylenic diols, diplynes A and C (Figure 1.2) which were isolated from the Philippines sponge Diplastrella sp. The work contained herein represents the first total synthesis of diplynes A and C. All the compounds isolated from Diplastrella sp. have shown activity in the HIV-1 integrase inhibition assay. The pathway envisioned for the synthesis of diplyne A (1) involved a Sonogashira cross coupling reaction to couple a terminal acetylene 9 with 1,2-dibromoethylene 10, forming the left hand portion of the molecule. The right hand portion was produced through a Cadiot-Chodkiewicz coupling of a terminal acetylene 12 with the bromo-alkyne 11. The synthesis of diplyne C 3 followed a similar strategy, with a Cadiot-Chodkiewicz coupling on the right hand fragment. The left hand fragment of the molecule was assembled through a hydroboration-mercuration-bromination procedure, producing stereoselectively the trans isomer.