- A new synthesis of potent antitumor saponin OSW-1 via Wittig rearrangement
-
OSW-1 and its analogues in which thiophene ring was introduced at the side chain were synthesized employing Wittig rearrangement of 17E(20)-ethylidene-16α-(4′-methyl-2′-thienyl)methyloxy steroid. The synthesis required nine steps from the known 17E(20)-ethylidene-16α-hydroxy steroid in 15.6% overall yield.
- Tsubuki, Masayoshi,Matsuo, Sohichiro,Honda, Toshio
-
-
Read Online
- OSW Saponins: Facile synthesis toward a new type of structures with potent antitumor activities
-
OSW saponins, featuring a 16β,17α-dihydroxycholest-22-one aglycon and an acylated β-D-xylopyranosyl-(1→3)-α-L- arabinopyranosyl residue attached to the 16-hydroxyl group, have recently been discovered from a group of lily plants, which show potent antitumor activities with a novel mechanism of action. This paper describes an aldol approach to the stereoselective construction of the 16α,17α-dihydroxycholest-22-one structure from 16α-hydroxy-5-androsten-17-ones and propionates. Elaboration of the aldol adducts toward OSW-1, involving installation of the isoamyl ketone side chain, inversion of the 16-hydroxyl configuration, and selective protection of the C22-oxy function, has been explored and accomplished. In particular, the present route was found convenient for the synthesis of OSW saponin analogues with a C22-ester side chain. Thus, the 23-oxa-analogue of OSW-1 (40) was prepared starting from the industrial dehydroisoandrosterone (1) in a linear eight-step sequence and in 26% overall yield. Analogues with a variety of modified side chains were prepared, via aldol condensation with propionates of varying length, thiopropionate, and acetate (for preparation of 68-75) or via aminolysis of the 22,16-lactone 26 (for preparation of the 23-N-analogues). Cross metathesis (CM) reaction was also found feasible for modification at the final stage from C22-allyl ester 70. Valuable structure-activity relationships (SAE), together with the practical synthetic approach, have thus been provided to set a new stage for further studies on this new type of antitumor structures.
- Shi, Bingfeng,Tang, Pingping,Hu, Xiaoyi,Liu, Jun O.,Yu, Biao
-
p. 10354 - 10367
(2007/10/03)
-
- Synthesis of analogues of a potent antitumor saponin OSW-1
-
A series of side chain analogues (5a-e), a 22-glycosylated isomer (10), and 16β-O-L-arabinosyl (13a) or 16β-O-D-xylosyl (13b) analogues of OSW-1 were synthesized. All analogues were found to be less cytotoxic against breast and endometrial cancer cell lines than the natural product.
- Morzycki, Jacek W.,Wojtkielewicz, Agnieszka,Wolczynski, Slawomir
-
p. 3323 - 3326
(2007/10/03)
-
- Synthesis of a cholestane glycoside OSW-1 with potent cytostatic activity.
-
The potent antitumor agent OSW-1 was synthesized from the protected aglycone in different ways. It was proven that direct glycosylation of the aglycone in its hemiketal form could be achieved, affording the protected OSW-1 in a moderate yield. Alternatively, regioselective protection of the triol obtained by reduction of the aglycone, followed by glycosylation, deprotection and oxidation yielded the same OSW-1 derivative. The third approach to this compound consisted of glycosylation of the previously described lactol [Morzycki, J. W.; Gryszkiewicz, A. Polish J. Chem. 2001, 75, 983-989], reaction of the resulting aldehyde with a Grignard reagent, and oxidation. OSW-1 obtained on removal of the protective groups was identical with the natural product.
- Morzycki, Jacek W,Wojtkielewicz, Agnieszka
-
p. 1269 - 1274
(2007/10/03)
-
- Total synthesis of the anticancer natural product OSW-1
-
The highly potent anticancer natural saponin OSW-1 has been successfully synthesized from commercially available 5-androsten-3β-ol-17-one 79 in 10 operations with 28% overall yield. The key steps in the total synthesis included a highly regio- and stereoselective selenium dioxide-mediated allylic oxidation of 80 and a highly stereoselective 1,4-addition of α-alkoxy vinyl cuprates 68 to steroid 17(20)-en-16-one 12E to introduce the steroid side chain. This total synthesis demonstrated once again the versatile synthetic applications of α-halo vinyl ether chemistry developed in our laboratories.
- Yu, Wensheng,Jin, Zhendong
-
p. 6576 - 6583
(2007/10/03)
-
- First total synthesis of an exceptionally potent antitumor saponin, OSW- 1
-
OSW-1 (1), an acylated disaccharide cholestane saponin from Ornithogalum saudersiae with exceptionally potent antitumor activity, was first synthesized from commercially available dehydroisoandrosterone, L-arabinose, and D-xylose in total 27 steps with the longest linear sequence of 14 steps and in 6% yield.
- Deng, Shaojiang,Yu, Biao,Lou, Yun,Hui, Yongzheng
-
p. 202 - 208
(2007/10/03)
-
