Deoxypancratistatin

Hudlicky, T., Tian, X., Konigsberger, K., Mauiya, R., Rouden, J. and Fan, B. (1996c) Toluene-dioxygenase-mediated as-dihydroxylation of aromatics in enantioselective synthesis. Asymmetric total syntheses of pancratistatin and 7-deoxypancratistatin, promising antitumor agents. J. Am. Chem. Soc., 118, 10752-10765. 

Conversion of 77 into the O-benzylhydroxamicacid derivative 78 followed by O-desilylation and oxidation of the resulting lactol furnished the lactone 79. The trifluoroacetamide 80 obtained by successive treatment of 79 with samarium (II) iodide and acidic Dowex resin, on exposure to methanolic potassium carbonate generated, (+)-7-deoxypancratistatin (67). The overall yield of the alkaloid starting from D-gulonolactone was 7%. 

Scheme 11. Synthesis of (+)-7-deoxypancratistatin (continued next page).

A 6-exo-trig cyclization of a pyran derived radical onto an oxime has been employed as the key step in the synthesis of Amaryllidace alkaloid (+)-7-deoxypancratistatin [95JA7289], Treatment of 202 under reductive cyclization conditions gave 203 as a single stereoisomer in good yield. The compatibility of the radical reaction conditions with the dense functionality present in 202 is noteworthy. 

Acidic hydrolysis of MOM ethers is not easy 3% concentrated HQ in aqueous EtOH and trifluoroacetic acid in dichloromethane at room temperature are typical conditions taken from the solo synthesis of Pleuromutilin by Gibbons [Scheme 4.238J.444 At the other extreme are the remarkably easy scission of a phenolic MOM group activated by an adjacent carbonyl in Muxfeldfs synthesis of Terramycin [Scheme 4.239J44-15 and the use of an acidic exchange resin in re-fluxing methanol to cleave a MOM ether and a dioxolane used in a synthesis of 7-deoxypancratistatin [Scheme 4.240].446... 

FIGURE 1.11 Compounds synthesized from sugars (i )-l-deuterioethanol (34), (-l-)-furanomycin (35), 7-deoxypancratistatin (36), and soraphen (37). 

The Lewis acid-catalyzed aza-Payne rearrangement was utilized in the total synthesis of ep/-7-deoxypancratistatin by T. Hudlicky and co-workers. The 2,3-aziridino alcohol was treated with f-BuLi, to generate the epoxy amide that was trapped with piperonyl bromide. 

Rinner, U., Siengalewicz, P., Hudlicky, T. Total synthesis of epi-7-deoxypancratistatin via aza-Payne rearrangement and intramolecular... 

Since the isolation and discovery of the significant biological activity of 7-deoxypancratistatin (210) and pancratistatin (211), which have more oxygenated functional substituents than lycoricidine (204), synthetic studies have been performed extensively. The total synthesis of optically active (-1-)-7-deoxypancratistatin (210) and (+)-pancratistatin (211) has been reported independently by four research groups. 

The synthesis of (-l-)-7-deoxy-fra s-dihydronarciclasine (208) and (-1-)-7-deoxypancratistatin (210) employing the key intermediate 221 previously reported in the synthesis of (-l-)-lycoricidine (204) 150) has been published by a fourth group 162) (Schemes 28 and 29). Catalytic hydrogenation of the protected 7-deoxylycoricidine 221, followed by conversion of the 2/3-0-(p-methoxy)phenylmethyl (MPM) group into a 2a-acetoxy substituent, produced the protected (-l-)-7-deoxy-rranj-dihydronarciclasine 254. Stepwise deprotection of 254 afforded (-t-)-7-deoxy-trans-dihydronarciclasine (208) (Scheme 28). 

D-Xylose has been used as starting material in the synthesis of (+)-Conduritol C [88] and cyclophellitol [56] (Scheme 12). The combinatitMi of the zinc-mediated tandem reaction with RCM was also used in the synthesis of 7-deoxypancratistatin, a naturally occurring compound with activities against different cancer types. In the latter synthesis, the longest reaction sequence involves 13 steps from o-xylose with a 4% overall yield [58] (Scheme 12). 

Scheme 12 Syntheses of (+)-conduritol C, cyclophellitol and 7-deoxypancratistatin using the two-step strategy reductive ring opening of 5-iodo-D-xylofuranoside and ring-closing metathesis...

Synthesis of (+)-7-Deoxypancratistatin. Different approaches to the total synthesis of (+)-7-deoxypancratistatin have been reported recently because of the promising biological properties shown by this alkaloid. An elegant synthesis of (+)-7-deoxypancratistatin has been achieved from furan and t runs-1,2-bis(phenylsulfonyl)ethylene (Eq. 155).265 This synthesis clearly illustrates the utility of alkenyl sulfones as Michael acceptors and dienophiles for cycloaddition reactions. 

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