Synthesis stigmasterol

Owing to periodic fluctuations in the price of diosgenin. alternative law materials such as solasodinc have been used for the synthesis of steroid drugs. In the U.S., the plant sterols stigmasterol and /3-sitosterol arc a significant raw material for the synthesis of antiinflammatory glucocorLicuids and other steroid hormones. 

Progesterone is a hormone, secreted by the corpus luteum, that is involved in the control of pregnancy. Its structure was established, in part, by the following synthesis from the steroid stigmasterol, obtained from soybean oil. 

SITOSTEROL Sitosterol is another phytosterol and is an analogue of stigmasterol with a saturated side chain. It is obtained from soy oil and com oil. The side chain cannot be degraded chemically, but microbiologically it is possible to produce intermediates of valne to the steroid industry. Sitosterol can therefore be used as a starting material for the synthesis of steroid hormones. 

Before discussing our synthetic studies, mention should be made of different approaches employed in the synthesis of brassinolide by other investigators. The most practical method would be to start with a readily available steroid having the same carbon skeleton as brassinolide, and then introduce the required functional groups in rings A and B and the sidechain. In the case of 28-homobrassinolide (5), tiie ideal starting compound would be the abundant sterol stigmasterol (4). 

A more widely used approach to brassinolide is reaction of a C-22 aldehyde, derived from stigmasterol, with a carbanion containing a double bond (or potential double bond). In nearly all cases, epoxidadon of die double bond was employed to introduce one or both oxygen functions (17-24). A synthesis of the brassinolide sidechain starting from pregnenolone has also been reported (25). 

Our first synthesis of brassinolide started from stigmasterol which was converted to (20S)-6p-methoxy-3a,5-cyclo-5a-pregnane-20-carboxaldehyde (2). This pathway involved formation of the mesylate with methanesulfonyl chloride in pyridine and tetrahydrofuran, treatment of the mesylate with potassium acetate in methanol, and ozonolysis of die i-sterol with reductive work-up. 

This brief review covers the period of the last ten years in the development of brassinosteroid chemistry in our laboratory. Our interest has been focused on the synthesis of natural brassinosteroids (brassinolide, homobrassinoli-de, epibrassinolide, norbrassinolide, etc.), their analogues and intermediates starting from stigmasterol, ergosterol, or pregnenolone. Some aspects of biological activity are discussed. 

Synthesis of BS from stigmasterol. For our purpose commercially available stigmasterol 1 was attractive as a starting material because its 3 -hydroxy-5-ene functionality permitted the necessary transformations of the cyclic part and the side chain. The conversion of 1 into natural BS was achieved using two different strategies a) with the retention of the carbon skeleton for the synthesis of C29 derivatives and b) via the 022... 

In 1982, we reported two different syntheses of brassinolide (30) from stigmasterol.66,67 The second synthesis,67 whose full paper was published in 1984,68 was later extended to a successful synthesis of 30 g of brassinolide in 7.0% overall yield from stigmasterol (Figure 2.23).69-71... 

Insects, unlike most vertebrates and plants, lack the capacity for de novo sterol synthesis and require dietary sterol for their normal growth, development and reproduction. This sterol requirement is in most cases satisfied by cholesterol (86) which is one of the principal sterols in insects, serving as component of the cell membranes and as a precursor of ecdysone (107). The zoophagous species such as the house fly Mucosa domestica are unable to convert phytosterol to cholesterol. For this reason, cholesterol is an essential nutrient for these species. In phytophagous and omnivorous insects, sterols such as sitosterol (87), campesterol (88), and stigmasterol (89) are dealkylated to cholesterol. Thus, 24-dealkylation is one of the essential metabohc processes in phytophagous insects (Fig. 15). 

The synthesis of a-ecdysone was developed almost at the same time by several research groups working independently. The processes of Kerb et al. (Kerb et al., 1966 Wiechert et al., 1966) and Siddall et al. (1966) both start from 23,24-dinorcholenic acid (90), obtained by the oxidative cleavage of the side chain of stigmasterol 91. 

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