Studies directed towards synthesis of the mitoenes : chemistry and synthesis of appropriately functionalized perhydroazocines and their conversion to functionalized pyrrolizidines.

Bibliographic Details
Main Author: Yerino, Lario Vincent
Other Authors: Hogg, John L. (degree committee member.)
Format: Thesis Book
Language:English
Published: 1981.
Subjects:
Online Access:Link to ProQuest Copy
Link to OAKTrust copy

MARC

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099 |a 1981  |a Dissertation  |a Y47 
100 1 |a Yerino, Lario Vincent. 
245 1 0 |a Studies directed towards synthesis of the mitoenes :  |b chemistry and synthesis of appropriately functionalized perhydroazocines and their conversion to functionalized pyrrolizidines. 
264 1 |c 1981. 
300 |a xii, 134 leaves :  |b illustrations ;  |c 29 cm 
336 |a text  |b txt  |2 rdacontent 
337 |a unmediated  |b n  |2 rdamedia 
338 |a volume  |b nc  |2 rdacarrier 
500 |a "Major subject: Chemistry." 
500 |a Typescript (photocopy). 
500 |a Vita. 
502 |b Ph. D. in Philosophy  |c Texas A & M University  |d 1981 
504 |a Includes bibliographical references (leaves 88-92). 
520 3 |a The mitosenes (mitomycin analogs lacking the 9a-methoxy group) possess antiviral and antibacterial activity. Structurally they are centered around a pyrrolizidine BC-ring bearing a carbamate terminated side chain, a functionalized quinone A-ring, and an aziridine D-ring. Due to their therapeutic potential and interesting structural features, we have undertaken studies directed towards the development of synthetic methodology which might be useful in the preparation of members of this class of compounds. During the course of these studies we have developed methods for the preparation of highly substituted pyrrolizidines bearing the necessary functionality for use as precursors in the total synthesis of the mitosenes. The pyrrolizidines were generated by transannular cyclization of functionalized perhydroazocines which were obtained by reaction of appropriately 1-blocked-1,2-dihydropyridines with electron deficient acetylenes. Efficient methods for synthesis of the requisite acetylenes t-butyl 2-methyl-4-oxo-7-hydroxyhept-5-ynoate tetrahydropyranyl ether and n-butyl 2-methyl-4-oxo-7-dimethyl-t-butylsilyloxyhept-5-ynoate from succinic anhydride were developd. This approach allowed for selective differentiation of the succinoyl carbonyls at various stages of the synthesis. The acetylenes were reacted with 1-styryl-1,2-dihydropyridine to give 3-{t-butyl 2-methylsuccinoly}-4-tetrahydropyranyloxymethyl-1-styryl-1,8-dihydroazocine and 3-{n-butyl 2-methylsuccinoyl}-4-dimethyl-t-butylsilyloxymethyl-1-styryl-1,8-dihydroazocine. These azocines were then reacted with ozone followed by catalytic hydrogenation to give 3-{t-butyl 2-methylsuccinoyl}-4-hydroxymethyltetrahydropyranyloxymethyl-1-formyl-1,6,7,8-tetrahydroazocine and 3-{n-butyl 2-methylsuccinoyl}-4-dimethyl-t-butylsilyloxymethyl-1-formyl-1,6,7,8-tetrahydroazocine, the major compounds of study. ... 
650 0 |a Mitomycin C. 
650 0 |a Pyrrolizidines. 
650 4 |a Chemistry 
655 7 |a Academic theses  |2 lcgft 
700 1 |a Hogg, John L.,  |e degree committee member. 
700 1 |a Mariano, P. S.,  |e degree supervisor. 
710 2 |a Texas A & M University,  |e degree granting institution. 
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