Drug synthesis partial routes

Although all the main classes of steroids have now been attained by total synthesis, most drugs are in fact, as noted above, prepared by partial synthesis from natural products that contain the steroid nucleus. The bulk of the world s supply of steroid starting material is derived by differing chemical routes from only two species of plants the Mexican yam, a species of... 

Once the structure of a lead has been decided it is necessary to design a synthetic pathway to produce that lead. These pathways may be broadly classified as either partial or full synthetic routes. However, partial synthetic routes tend to be more concerned with the large scale production of proven drugs rather than the synthesis of lead compounds. This chapter is intended to introduce some of the strategies used, and the challenges associated with the design of these synthetic routes. 

Although total asymmetric syntheses of topotecan 4 and irinotecan 5 as well as homocamptothecin 14 have been reported [58], these drugs can be preferentially prepared by short semisynthetic routes starting from natural CPT. For example, SmithKline Beecham developed a synthesis of topotecan 4 from 10-hydroxy-CPT 32 [110]. This intermediate is obtained with 91% yield in two-step reduction-oxidation process involving an initial Pt-catalyzed partial hydrogenation to tetrahydroquinoline intermediate 31 and its subsequent oxidation with the use of Phl(OAc)2 [110]. Condensation of 10-hydroxy-CPT with formaldehyde and... 

In the pursuit of new cardiotonic drugs, chemists have extensively explored the synthesis and semisynthesis of various members of the cardenolide family. The approaches based on partial synthesis starting with androstane/ pregnane derivatives have been by far the most explored tactics. However, these routes have significant limitations as the available androstanes and pregnanes lack oxygenation at the key positions of the steroid skeleton... 

Synthetic highlights The partial synthesis of paclitaxel was necessary to enhance the availability of the drug substance and avoid unsustainable use of yew trees. Many different synthetic routes have been reported and three inventive pathways for the enantioselective or site-selective approaches to various segments of the paclitaxel molecule are described. These are aU promoted by organometal catalytic complexes. Reactions presented include use of the intramolecular Heck reaction in the synthetic pathway to baccatine III the Sharpless reaction and the introduction of a trifunctional catalyst for biomimetic synthesis of chiral diols synthesis of the paclitaxel side-chain and use of a Zr-complex catalyst in the reductive N-deacylation of taxanes to primary amine, the key precursor of paclitaxel. 

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