초록

An efficient process is described for the synthesis of 5, a key intermediate for the synthesis of the potent antitumor agents ecteinascidin 743 (1) and phthalascidin (2) from the readily available building blocks 3b and 4.

대표청구항 ▼

1. The process of Scheme 1, comprising the steps of:(a) combining the compound 3b:with the amino lactone 4:in the presence of an acylating reagent to form the coupled product 6:(b) treating compound 6 with an allyl bromide to give amide 7:(c) reduction of the lactone compound 7 to the corresponding

1. The process of Scheme 1, comprising the steps of:(a) combining the compound 3b:with the amino lactone 4:in the presence of an acylating reagent to form the coupled product 6:(b) treating compound 6 with an allyl bromide to give amide 7:(c) reduction of the lactone compound 7 to the corresponding lactol, compound 8:(d) desilylation of compound 8 to compound 9:(e) cyclization of compound 9 to compound 10:(f) reduction of the lactam in compound 10 to the corresponding cyclic aminal which upon exposure to HCN provided the pentacyclic amino nitrile, compound 5: 2. The process of Scheme 2, comprising the steps of:(a) conversion of the compound 11:to the mono L-butyldimethylsilyl (TBS) ether, compound 12:(b) etherification with methoxymethyl chloride to yield compound 13:(c) cleaving the N-allyloxycarbonyl and O-allyl groups in 13 gives the secondary amine, compound 14:(d) N-methylation of compound 14 affords compound 15:(e) C-methylation of compound 15 affords compound 16:(f) acetylation of phenol 16 affords the corresponding acetate, compound 17:(g) desilylation of compound 17 yields the primary alcohol, compound 18:(h) Mitsunobu displacement of the primary hydroxyl of 18, yields the phthalimide, compound 19:(i) acid-catalyzed cleavage of the methoxymethyl ether in compound 19, generates compound 2-phthalascidin: 3. The synthetic intermediate of Scheme 1-compound 6: 4. The synthetic intermediate of Scheme 1-compound 7: 5. The synthetic intermediate of Scheme 1-compound 8: 6. The synthetic intermediate of Scheme 1-compound 9: 7. The synthetic intermediate of Scheme 1-compound 10: 8. The synthetic intermediate of Scheme 2-compound 12: 9. The synthetic intermediate of Scheme 2-compound 13: 10. The synthetic intermediate of Scheme 2-compound 14: 11. The synthetic intermediate of Scheme 2-compound 15: 12. The synthetic intermediate of Scheme 2-compound 16: 13. The synthetic intermediate of Scheme 2-compound 17: 14. The synthetic intermediate of Scheme 2-compound 18: 15. The synthetic intermediate of Scheme 2-compound 19: