Reverse transcriptase other conditions

R-(R, S )]-p-Methyl-a-phenyl-1-pyrrolidineethanol is an important chiral mediator for the enantioselective addition of an acetylide to a prochiral ketone.2 3 This reaction has been successfully applied to the synthesis of the reverse transcriptase inhibitor efavirenz (DMP-266) (Scheme 1).3.4 Preparation of the enantiomer, (1S,2R)-N-pyrrolidinylnorephedrine, has been reported.2 The method used potassium carbonate (K2CO3) as base, but the yield of the product was only 33%. The submitters have extensively studied the formation of the pyrrolidinyl ring under various conditions as summarized in Table I. Eventually they found that the reaction was extremely efficient when it was run in toluene using sodium bicarbonate (NaHCC>3) as base (entry 8, Table I),5 which gave [R-(R, S )]-p-methyl-a-phenyl-1-pyrrolidineethanol quantitatively. Enantioselective (up to 99% ee) addition of cyclopropylacetylene to the ketoaniline 1 is achieved when the solution of [R-(R, S )]-p-methyl-a-phenyl-1-pyrrolidineethanol is used as a chiral additive.3 In addition, this method is also applicable to the preparation of a variety of alkylated norephedrines and other amino alcohols in excellent yields as Illustrated in Table II. These amino alcohols are potentially useful in asymmetric syntheses. 

The success of AZT in ameliorating the condition and prolonging the life of AIDS patients has stimulated intense efforts to discover other nucleosides with equal or better efficacy. As a result of these efforts, literally dozens of nucleoside analogues have been reported to inhibit HIV in vitro Of these, only a few have entered clinical trials and, at this time, only 2, 3 -dideoxyinosine has achieved FDA approval. The mechanism of action of these nucleosides involves anabolism to their 5 -triphosphates which can act as inhibitors of the viral reverse transcriptase and/or be incorporated into the viral DNA where they lead to chain termination. 

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