The cyclopentyl compounds 113,114, and 115 and their enantiomers ent-113, ent-114 and ent-115 represent valuable chiral building blocks for the synthesis of steroids and triterpenoids. These compounds are readily available in chiral form from the Grob type cleavage of (+)-9,10-dibromocamphor (120) or (-)-9,10-dibromocamphor (ent-120) respectively.
The hydroxyacid 114 was transformed into the bicyclic ester 153 in a series of seven steps, the key step of which was the intramolecular Friedel-Crafts acylation of the methylene diacid 161. The ester 153 is considered to be a valuable steroidal CD synthon, incorporating functionality for introduction of both the A and B rings and a C(20) sidechain. It was demonstrated that it was possible to alkylate the ketal 169 stereospecifically and convert the product to the enone 168 in which the steroidal C(20) centre has been established with the natural R configuration.
In a second approach to steroidal precursors, the hydroxydiene 299 was prepared in six steps from the bromoester 115. The enantiomer of 299, (ent-299) represents a potentially useful intermediate in the intramolecular Diels-Alder route to A-aromatic steroids such as estrone (3), and would be readily available from ent-115.
The bromoester ent-115 and (+)-5,6-dehydrocamphor (223) were combined in a synthesis of the tetracyclic hydroxyenone 252, the key step of which was the anionic oxy-Cope rearrangement of the 5,6-dehydrocamphor derivative 241. The structure 252 is considered to represent the basic tetracyclic skeleton of euphane and apo-euphane triterpenoids, and posesses suitable functionality for incorporation of methyl groups at C(10) and C(8) (apo-euphane) or C(14) (euphane), as well as oxygen substituents at those centres at which it is commonly found in the triterpenoids.
Finally, a mechanistic investigation of the rearrangement of 2-methylenebornane (314) to 4-methylisobornyl acetate (315) is described. The methyl region of the ¹H NMR spectrum of 4-methylcamphor (308), derived from 314, was unambiguously assigned by a series of NMR
experiments and used to trace the fate of deuterium when 2-(dideuteriomethylene)bornane (323) and 8-deuterio-2-methylenebornane (324) were subjected to the rearrangement conditions. [formulas omitted] / Science, Faculty of / Chemistry, Department of / Graduate
| Identifer | oai:union.ndltd.org:UBC/oai:circle.library.ubc.ca:2429/30990 |
| Date | January 1990 |
| Creators | Clase, Juha Andrew |
| Publisher | University of British Columbia |
| Source Sets | University of British Columbia |
| Language | English |
| Detected Language | English |
| Type | Text, Thesis/Dissertation |
| Rights | For non-commercial purposes only, such as research, private study and education. Additional conditions apply, see Terms of Use https://open.library.ubc.ca/terms_of_use. |
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