Date of Award
Doctor of Philosophy
Luis E. Martinez
This research focuses on the combinatorial solid phase organic synthesis (SPOS) of different bioactive compounds utilizing transition metal mediated reactions via microwave assisted organic synthesis (MAOS).
A microwave-assisted solid-supported Dötz benzannulation of chromium Fischer carbene complexes with various alkynes has been reported. The oxidative cleavage of the resulting resin-bound 1,4-naphthols affords 2,3-disubstituted-1,4-naphthoquinone derivatives in good to moderate yields with high purities. We demonstrated that solid phase organic synthesis of naphthoquinones via conventional heating is limited due to their long reaction times and high temperatures. The products decompose leading to low yields and purities.2 Microwave assisted synthesis of these naphthoquinones will increase the yields, reduce reaction times, temperatures and avoid decomposition of the products leading to new probes for chemical biology.
The previously reported synthesis procedure demands considerable effort and care to avoid decomposition of the intermediates. Furthermore, contemporary synthesis of Fischer carbene complexes is limited by purification using column chromatography. A novel "Catch-Release" technique of Fischer carbene chromium complex has been accomplished to purify the organometallic complex. This technique produces both solid supported and solution phase Fischer carbene complexes with good to moderate yields and high purities. The application of solid supported reagents will eliminate the need for column chromatography or liquid-liquid purifications thus provides a new synthetic approach to these types of organometallic moieties. The first "Catch-Release" synthesis of both solid- and non-supported chromium Fischer carbene complexes is presented.
Finally, "Click Chemistry" offers a versatile strategy for the construction of heterocyclic compounds that find wide spread applications in drug discovery programme. In particular, Huisgen 1,3-dipoar cycloaddition of alkynes with azides to give triazole derivatives is a powerful example of this chemistry. An efficient method for the solid-phase organic synthesis of 1, 2, 3-triazole containing 1,4-naphthoquinone derivatives through solid-supported Dötz benzannulation and Huisgen 1,3-dipolar cycloaddition reaction, followed by the oxidative cleavage of the resulting resin-bound click product is described.
Received from ProQuest
Garcia-Martinez, Israel, "Microwave Assisted Solid-Supported Organic Synthesis: A Novel Methodology To Obtain 2,3-Disubstituted-1,4-Naphthoquinones" (2009). Open Access Theses & Dissertations. 2679.