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作者 Hogan, Philip C
書名 Enantioselective synthesis of kedarcidin chromophore aglycon
國際標準書號 0496791087
book jacket
說明 303 p
附註 Source: Dissertation Abstracts International, Volume: 65-05, Section: B, page: 2419
Adviser: Andrew G. Myers
Thesis (Ph.D.)--Harvard University, 2004
An enantioselective synthesis of kedarcidin chromophore aglycon in differentially protected form (26) is described. The route is 25 steps in the longest linear sequence, with an average yield of 82% per step (overall yield 1%).*
The key step in the sequence was the transannular cyclization of the bromoenetriyne 28, induced by lithium-halogen exchange, affording the ansa-bridged bicyclo[7.3.0]dodecadienediyne 56. Silyl ether cleavage followed by hydroxyl-directed epoxidation and hydroxyl protection transformed 56 into the epoxide 59. Completion of the synthesis of 26 was achieved by dehydration of 59 in the presence of Martin sulfurane.*
Several of the intermediates in this route (e.g., 51 and 59) as well as the protected aglycon (26) exhibited conformational isomerism on the NMR time scale, attributed to hindered rotation of the chloropyridine ring (atropisomerism). The kinetics and thermodynamics of these processes were studied in detail. Kedarcidin chromophore aglycon ( 26) was observed to undergo cycloaromatization rapidly at ambient temperature in the presence of good hydrogen-atom donors, providing the epoxide 60 as a single atropisomer. These results suggest that atropisomeric forms of kedarcidin chromophore (1) are interconvertible at ambient temperature, and that 1 is capable of cycloaromatization at ambient temperature without chemical activation
*Please refer to dissertation for diagrams
School code: 0084
DDC
Host Item Dissertation Abstracts International 65-05B
主題 Chemistry, Organic
0490
Alt Author Harvard University
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