Synthesis and Pharmacological Properties of Modified A- and D-Ring in Dehydroepiandrosterone (DHEA): A Review

Dehydroepiandrosterone (3 beta-hydroxyandrost-5-en-17-one) (DHEA) is a naturally occurring steroid hormone primarily produced in the zona reticularis of the human adrenal glands. It serves as a crucial precursor for sex hormones, such as testosterone, estradiol, and androstenedione. Recent findings indicate that DHEA serves as the primary source of sex steroids in women during both pre- and postmenopausal stages. Additionally, a decline in DHEA levels with age is linked to various hormone-deficiency symptoms. Despite the wide array of biological activities that make DHEA a valuable polycyclic natural steroid, particularly for pharmaceutical and cosmetic applications, reports suggest that oral DHEA has limited clinical effect. Thus, A- and D-ring modified DHEA are synthesized and their biological activities are carried out by different research groups and enhanced biological activity reported in the literature. Here, in this review, we have tried to cover all of the synthetic routes and biological studies of modified A- and D-ring DHEA from 2015 to mid-2022.