Synthetic Approach to the Core Structure of Oleandrin and Related Cardiac Glycosides with Highly Functionalized Ring D

Abstract

The first synthetic approach to the core structure of cardiac glycoside oleandrin exhibiting a potent cytotoxic activity, starting from a common androstane derivative, has been accomplished. The synthesis is focused on stereoselective transformations in the densely substituted and sterically shielded five-membered ring (steroid ring D). The developed synthesis paves a route to the synthesis of related bufadienolides, i.e., constituents of traditional drug Ch'an Su, bufotalin, and cinobufagin.

An efficient synthesis of 3β,14β-dihydroxy-5α-androst-15-en-17-one

“…Characteristic 1 H chemical shifts of C16-H, C15-H, C18-CH 3 , C19-CH 3 and C3a-H unequivocally revealed the specific chemical environment of these protons in compound 4a. The 1 H-decoupled 13 C NMR spectrum of compound 4a showed 19 distinct signals in agreement with the suggested structure. The important signals which were assigned to the CO and one C=C double bond appeared at d = 222.54, 153.54, and 112.86 ppm.…”

“…The 1 H NMR spectrum of compound 4a 1 showed two doublet signals at 7.91 (d, J = 5.8 Hz, 1H) and 5.97 (d, J = 5.7 Hz, 1H) for C15-H and C16-H of the double bond, respectively. The important signals in the 13 C NMR which were assigned to the conjugated CO and two C=C double bonds, appeared at d = 212.40, 153.03, 139.29, 137.00 and 127.96 ppm.…”

“…This results in a slowing of the heart rate and a positive inotropic response, directly counteracting the effects of congestive heart failure.In addition, recent investigations have shown that 14β-hydroxysteroids possess a wide spectrum of biological activities including anticancer, 4,7,8 immunoregulatory, antiinflammatory and antihypertensive properties. [9][10][11] Recently, the drug-oriented design and synthesis of 14β-hydroxysteroids has received considerable attention important results include [12][13][14] the preparation of the 17a[(aminoalkoxy)imino] alkyl analogues of digitoxigenin by partial synthesis starting with androstane derivatives. These are potent inhibitors of Na + , K + -ATPase (Fig.…”

The Botanical Glycoside Oleandrin Inhibits Human T-cell Leukemia Virus Type-1 Infectivity and Env-Dependent Virological Synapse Formation

“…Oleandrin is a lipid-soluble, botanical cardiac glycoside comprised of: (1) the steroid aglycone, oleandrigenin, and (2) a sugar moiety (e.g., D-diginosyl) and its chemical structure is shown in Figure 1a [1,4,78]. To determine whether the purified oleandrin compound, or an extract of N. oleander , could inhibit HTLV-1 proviral replication and/or the production and release of p19 Gag -containing virus particles, the virus-producing HTLV-1-transformed SLB1 lymphoma T-cell-line [71] was treated with increasing concentrations of oleandrin or a N. oleander extract, or the sterile Vehicle control (20% DMSO in MilliQ-treated ddH 2 O) and then incubated for 72 h at 37°C under 10% CO 2 .…”

Control of the stereochemistry of C14 hydroxyl during the total synthesis of withanolide E and physachenolide C

“…2, eqn (2)). 28,29 Based on this information, we were condent that installation of the C-14 hydroxyl can be achieved from the a face, however, we discovered steric factors affecting the stereoselectivity of that epoxidation which we describe below.…”