Pregnenolone conjugates

Deletion of the 17a-hydroxy group similarly leads to an effective topical antiinflammatory agent. Treatment of 16a-methylpregnenolone (244) (obtained by conjugate addition of an organometallic to pregnenolone) sequentially with bromine and acetate ion affords the 21 acetate, 245 (see, for example, the transformation of 196 to 198). In an interesting variation on the method for the introduction of a fluorine atom at 6, the... 

This enzymic conversion involves two enzymes, a dehydrogenase and an isomerase. The dehydrogenase component oxidizes the hydroxyl group on pregnenolone to a ketone, and requires the oxidizing agent cofactor NAD+ (see Box 11.2). The isomerase then carries out two tautomerism reactions, enolization to a dienol followed by production of the more stable conjugated ketone. 

The synthesis of adrenal steroids is illustrated in Fig. 5.3.1. Cortisol, corticosterone, and aldosterone are formed by sequential hydroxylations and oxidoreductions from pregnenolone and progesterone. 17a-Hydroxypregnenolone (17HP) is a branchpoint constituent because it can be converted to cortisol or adrenal androgens. All of the components of this pathway can be quantified by MS/MS. The steroids around the periphery are urinary metabolites and these are measured by GC-MS following hydrolysis of conjugates and derivatization. 

Drew, J., Letellier, M., Morand, P., and Szabo, A.G.. Synthesis from pregnenolone of fluorescent cholesterol analogue probes with conjugated unsaturation in the side chain, J. Org. Chem.. 51, 4047,... 

Sulfotransferases from tumoral and normal adrenals were shown capable of conjugating many steroids in vitro pregnenolone, 17-hydroxypreg-nenolone, corticosterone, deoxycorticosterone, testosterone, as well as the adrenal androgens were readily sulfated (Gual et al., 1962 Cohn et al., 1963 Lebeau and Baulieu, 1963 Adams, 1964 Bostrom et al., 1964 Killinger and Solomon, 1965). Indirect evidence, obtained from isotopic dilution studies, pointed to a possible secretion of pregnenolone sulfate... 

Figure 7 shows the transformations and conjugations of 21-hy droxy-pregnenolone in the fetal and placental compartments. 

Fig. 18. Schematic representation of the principal transformations of the Cu and Cl steroids and their conjugates in the fetal and placental compartments. Aj-P pregnenolone P progesterone ITd-IlO-Aj-P iTa-hydroxyprcgnenolone 17a-HO-P 17a-hydroxyprogesterone DTI A dehydroepiandrosterone AND androstenedione 17/J-.D1I-DHA androstenediol-lTp DIIA-S dehydroepiandrosterone sxilfate Ida-IIO-DHA 16a-hydroxydchydrocpiandrosterone 16 -1I0-D1IA-S 16a-hydroxydehydroepi-androstcrono sulfate androstenetriol-S androstenetriol sulfate E estriol Kj-S estriol sulfate T testosterone Ej estradiol Kj-S estradiol sulfate E[ estrone E -S estione sulfate.

Pregnenolone sulfate is princip iy secreted from the fetus to the placenta in this compartment most of this conjugate is hydrolyzed and transformed into progesterone, and a small part crosses to the mother as... 

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