First total synthesis of the novel brominated polyacetylenic diol (+)-diplyne a and (+)-diplyne c

by Gibeau, Craig R.

First Total Synthesis of the Novel Brominated Polyacetylenic Diol (+)–Diplyne A and (+)–Diplyne C By Craig R Gibeau 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 bromoalkyne 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. First Total Synthesis of the Novel Brominated Polyacetylenic Diols (+)–Diplyne A and (+)–Diplyne C A Thesis Submitted to the Faculty of Miami University in partial fulfillment of the Requirements in the degree of Masters of Science Department of Chemistry and Biochemistry By Craig Gibeau Miami University Oxford, Ohio 2005 Advisor: _____________________________ Professor Benjamin Gung Reader: _____________________________ Professor Richard Taylor Reader: _____________________________ Professor James Hershberger Reader: _____________________________ Professor Hongcai Zhou