Dehydroepiandrosterone synthesis

Ozonization of A -steroids usually gives complex mixtures (however, see ref. 48). Ozonolysis became a practical step in the general synthesis of B-norsteroids with the discovery that added methanol" (or formaldehyde ) improves yields significantly. Thus, Tanabe and Morisawa prepared 5/ -hydroxy-6/ -formyl-B-norsteroids (74) from cholesterol acetate, dehydroepiandrosterone acetate and pregnenolone acetate in overall yields of 64-74% by the reaction sequence represented below. 

Miller WL. Disorders of androgen synthesis—from cholesterol to dehydroepiandrosterone. Med Princ Pract. 2005 14(suppl l) 58-68. 

Figure 8-2. Synthesis of the steroid hormones. The rings of the precursor cholesterol are lettered. Dihydrotestosterone is produced from testosterone by reduction of the C - C double bond in ring A. DHEA = dehydroepiandrosterone.

Diagrammatic representation of zone-specific steroid synthesis in the adrenal cortex. All three zones can convert cholesterol into pregnenolone, but because of the presence/absence of certain enzymes, the flow of pregnenolone is preferentially directed to the synthesis of the steroid for which the particular zone is specific. It has not been determined whether the zona fasciculata produces dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulphate (DHEAS) in physiologically significant amounts. 

Hydroxypregnenolone acetate affords dehydroepiandrosterone quantitatively on treatment with lead tetra-acetate and calcium carbonate, and a remarkably simple synthesis of A -20-ketones is available by treatment of 17,21-diacyloxy-20-ketones with potassium acetate in hot DMF. The yield of A -steroid from prednisolone 17,21-diacetate was almost quantitative and the method is applicable to other esters and 4-en-3-ones. 

FIGURE 12.1 Biosynthesis of estrogens. Abbreviations DHEA, dehydroepiandrosterone El, estrone E2, estradiol T, testosterone DHT, dihydrotestosterone. Letrozole is an aroma-tase inhibitor, Finasteride is a 5a-reductase inhibitor. Androstane-3p,17P-diol (SPO) is an estrogenic steroid and its synthesis is blocked by 5a-reductase inhibitor, but not affected by aromatase inhibitor."... 

Fig. 9.1 Lipid systems affected in CNS disorders (shaded) and injuries (clear). Neurosteroid synthesis in the brain is affected in various brain disorders and injuries and treatment with neurosteroids (pregnenolone, dehydroepiandrosterone and allopregnanolone) showed positive trend in these brain pathologies (Fig. 9.3)...

F. 34.23. Synthesis of the steroid hormones. The rings of the precursor, cholesterol, are lettered. Dihydrotestosterone is produced from testosterone by reduction of the carbon-carbon double bond in ring A. Structural changes between the precursor and final hormone are noted in blue. DHEA = dehydroepiandrosterone. The dashed lines indicate alternative pathways to the major pathways indicated. The starred enzymes are those that may be defective in the condition congenital adrenal hyperplasia. 

Dehydroepiandrosterone (DHEA), a naturally occurring precursor of endogenous testosterone synthesis, assnmed national attention following its use in professional baseball. Unlike the parenteral administration of testosterone, however, DHEA does not produce a notable elevation in serum testosterone levels or enhance skeletal mnscle hypertrophy.Several adverse effects were reported and the International Olympic Committee considers DHEA an illegal steroid, banning its use. A recent analysis of sixteen commercial DHEA products revealed that only half the products contained the actual amount of DHEA stated on the product label, with actual levels varying between 0% and 150% of the label content. ... 

Wittig-Horner reaction. This phosphonate has been used in a synthesis of progesterone (4) from dehydroepiandrosterone (2). One step in the conversion of (3) into (4) was an Oppenauer oxidation. The usual conditions (aluminum... 

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