Natural products have been a rich source of agents of value in medicine. They have also inspired, at various levels, the fashioning of nonnatural agents of pharmaceutical import. Hitherto, these nonnatural derivatives have been primarily synthesized by manipulating the natural product. As a consequence of major innovations in the subscience of synthetic methodology, the capacity of synthesis to deal with molecules of considerable complexity has increased dramatically. In this paper, we show by example some total syntheses which draw from strategy-enabling advances in methodology. Moreover, we show how these capabilities can be used to discover and develop new agents of potential pharmaceutical value without recourse to the natural product itself.

Small molecule natural products in the discovery of therapeutic agents: the synthesis connection.

Publisher Summary This chapter discusses receptor-proteins for androgens and the mode of action of androgens on gene transcription in ventral prostate. The primary molecular processes by which hormones elicit their remarkable effects are still unclear. Historically, the study of the mechanism of action of hormones has followed very closely the advance in knowledge of the basic molecular processes operating in living organisms. It is quite natural that one of the most widely used approaches has been to study the effect of hormones on isolated enzymes. With few exceptions, the results have been rather disappointing. Generally, the effects were observable only under conditions unlikely to be physiological, or they could not be correlated with in vivo situations. In the search for the trigger mechanisms of hormones, one generally relies on the trial addition of hormones to an in vitro system believed to be the earliest event in a sequence of hormone effects in vivo. However, the in vivo time sequences for visible hormone effects may depend more on the relative time required to magnify each of the sequential events than on the true order in the initial chain of processes.

Receptor-proteims for androgens and the mode of action of androgens on gene transcription in ventral prostate.

Metabolism of levonorgestrel, norethindrone, and structurally related contraceptive steroids

Enantioselective synthesis of steroids

A Biological Classification of Progestational Agents

Von mehreren (±) 3-Oxy- und (±) 3-Methoxy-13-alkylgona-1,3,5(10)trien-17-onen und verwandten Verbindungen, einschliesslich von Vertretern der (±) 13-Alkylgon-4-en-3-on-Reihe, werden Totalsynthese und biologische Wirksamkeit beschrieben.

P. C. Phillips

Papers

Totally synthetic (±)-13-Alkyl-3-hydroxy and methoxy-gona-1,3,5(10)-trien-17-ones and related compounds

856. Totally synthetic steroid hormones. Part II. 13β-Alkylgona-1,3,5(10)-trienes, 13β-alkygon-4-en-3-ones, and related compounds