| Autor: |
Mickel, S. J., Niederer, D., Daeffler, R., Osmani, A., Kuesters, E., Schmid, E., Schaer, K., Gamboni, R., Chen, W., Loeser, E., Kinder, F. R., Jr., Konigsberger, K., Prasad, K., Ramsey, T. M., Repic, O., Wang, R.-M., Florence, G., Lyothier, I., Paterson, I. |
| Zdroj: |
Organic Process Research & Development; January 2004, Vol. 8 Issue: 1 p122-130, 9p |
| Abstrakt: |
The finale of the large-scale preparation of 60 g of the highly complex marine natural product, (+)-discodermolide (1), using a hybridized Novartis−Smith−Paterson synthetic route is presented. This contribution, which is the concluding part of a five-part series, highlights a reagent-controlled stereoselective boron enolate aldol reaction between 2 and 3 forming the C7 hydroxyl-bearing stereocenter, selective reduction of 4a to generate the 1,3-anti-diol 5, and a global deprotection and concomitant lactonization leading to (+)-discodermolide (1). A novel procedure for converting the minor epimeric aldol adduct 4b into discodermolide using a five-step sequence is also described. This large-scale synthesis of discodermolide involved 39 steps (26 steps in the longest linear sequence) and several chromatographic purifications and delivered sufficient material for early-stage human clinical trials. |
| Databáze: |
Supplemental Index |
| Externí odkaz: |
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