Tribute to John C. Martin at the Twentieth Anniversary of the Breakthrough of Tenofovir in the Treatment of HIV Infections

At Bristol-Myers (BM) (1985–1990), John C. Martin started his HIV career with directing the clinical development of didanosine (ddI) and stavudine (d4T). During this period, he became aware of the acyclic nucleoside phosphonates (ANPs), such as (S)-HPMPA and PMEA, as potential antiviral drugs. Under his impulse, BM got involved in the evaluation of these ANPs, but the merger of BM with Squibb (to become BMS) incited John to leave BM and join Gilead Sciences, and the portfolio of the ANPs followed the transition. At Gilead, John succeeded in obtaining the approval from the US FDA for the use of cidofovir in the treatment of cytomegalovirus (CMV) retinitis in AIDS patients, which was reminiscent of John’s first experience with ganciclovir (at Syntex) as an anti-CMV agent. At Gilead, John would then engineer the development of tenofovir, first as TDF (tenofovir disoproxil fumarate) and then as TAF (tenofovir alafenamide) and various combinations thereof, for the treatment of HIV infections (i), TDF and TAF for the treatment of hepatitis B (HBV) infections (ii), and TDF and TAF in combination with emtricitabine for the prophylaxis of HIV infections (iii).

Chemo- and regioselective ring-opening of donor–acceptor oxiranes with N-heteroaromatics

The first ring-opening of D–A oxiranes with N-heteroaromatics in a chemoselective C–C bond cleavage manner was achieved, providing acyclic nucleoside analogues containing a N-glycosidic bond. The Ganciclovir analogue could be obtained by reduction.

Diverse synthetic approaches towards C1′-branched acyclic nucleoside phosphonates

Acyclic nucleoside phosphonates (ANPs) represent a significant class of antiviral, anticancer, and antiprotozoal compounds. It is therefore highly desirable to have diverse synthetic routes leading towards these molecules. In the...

Introduction of a cyano group at the 2-position of an (R,S)-3-hydroxy-2-(phosphonomethoxy)propyl (HPMP) derivative of thymine elicits selective anti-HBV activity

The substantial impact of acyclic nucleoside phosphonates (ANPs) on human medicine encourages the synthesis of new ANP analogues with a potentially differentiated antiviral spectrum.