Acetylenic Inhibitors of C-22 Hydroxylase of Ecdysone Biosynthesis

The biosynthesis of steroids and triterpenoids

“…[1290][1291][1292] The cis-A/B ring junction appears to arise from a 3-oxo-4 -intermediate 1293 which is acted upon by a 5 -reductase: one possible reduction product of this enzyme, 14 -hydroxy-5 -cholest-7-ene-3,6-dione (5 -diketol; 111), was found to be efficiently converted to ecdysone (92) 1294 whereas 5 -cholest-7-ene-3,6-dione (5 -diketone; 112) was not, 1295 emphasising that 14 -hydroxylation is probably an early step in the biosynthetic sequence. Sequential 25-, 22R-and 2 -hydroxylation reactions constitute the later stages of ecdysteroid biosynthesis and suicide-substrate type acetylenic or allenic inhibitors have been designed to inhibit hydroxylations at each of C-25, [1296][1297][1298] C-22 [1297][1298][1299][1300][1301][1302][1303] and C-2. 1304 A variety of P-450 inhibitors were also observed to affect the 22-hydroxylase, suggesting that this is the most sensitive of the terminal hydroxylases towards inhibition.…”

Sterols that modify moulting in insects

“…They differ also in the stereochemistry at C-22. Our bioassay showed that inhibition increases with side chain length (see compounds [11][12][13][14] in Fig. 1 and Table 1).…”

STAT3 Inhibitory Activity of Structurally Simplified Withaferin A Analogues

“…Ketone 6 was to be prepared from hydrazone 8 using the aforementioned Shapiro reaction/Riley oxidation sequence. Finally, hydrazone 8 would be derived from known alcohol 9 , readily accessible from commercially available pregnenolone in two steps. , …”

“…Finally, hydrazone 8 would be derived from known alcohol 9, readily accessible from commercially available pregnenolone in two steps. 27,28 Our synthesis of SLW1 (3) commenced with the preparation of hydrazone 8 (Scheme 2). Silyl protection of alcohol 9 and subsequent saponification afforded alcohol 10 in 93% yield, which was then converted to enone 11 in 73% yield over three steps: (1) epoxidation of the trisubstituted olefin with m-CPBA, (2) oxidation of the C3 alcohol using PDC, and (3) epoxide opening under basic conditions.…”