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. 2006 Oct 27;71(22):8579-90.
doi: 10.1021/jo061650+.

Structure reassignment and synthesis of Jenamidines A1/A2, synthesis of (+)-NP25302, and formal synthesis of SB-311009 analogues

Jeremy R Duvall  1 , Fanghui Wu, Barry B Snider
Affiliations

Structure reassignment and synthesis of Jenamidines A1/A2, synthesis of (+)-NP25302, and formal synthesis of SB-311009 analogues

Jeremy R Duvall et al. J Org Chem. .

Abstract

The proposed structures of jenamidines A, B, and C (1-3) were revised to jenamidines A1/A2, B1/B2, and C (8-10). Jenamidines A1/A2 (8) were synthesized from activated proline derivative 43 by conversion to 26 in two steps and 50% overall yield. Acylation of 26 with acid chloride 38d gave 39d, which was deprotected with TFA and then mild base to give 8 in 45% yield from 26. (-)-trans-2,5-Dimethylproline ethyl ester (49) was prepared by the enantioselective Michael reaction of ethyl 2-nitropropionate (51) and methyl vinyl ketone (50) using modified dihydroquinine 60 as the catalyst. Further elaboration converted 49 to natural (+)-NP25302 (12). A Wittig reaction of proline NCA (76) with ylide 79 gave 72 as a 9/1 E/Z mixture in 27% yield, completing a one-step formal synthesis of SB-311009 analogues.

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Figures

FIGURE 1
FIGURE 1
Proposed structures of jenamidines A, B, and C.
SCHEME 1
SCHEME 1
Synthesis of Model 6
FIGURE 2
FIGURE 2
Bohemamine, NP25302, and revised structures of jenamidines A1/A2, B1/B2, and C.
SCHEME 2
SCHEME 2
Possible Late Steps in the Biosynthesis of Jenamidines A1/A2, B1/B2, and C
SCHEME 3
SCHEME 3
SCHEME 4
SCHEME 4
SCHEME 5
SCHEME 5
Synthesis of Intermediate 26
SCHEME 6
SCHEME 6
Synthesis of Jenamidine A1/A2 Model 31
SCHEME 7
SCHEME 7
Synthesis of Side-chain Acid Chlorides
SCHEME 8
SCHEME 8
Synthesis of Jenamidines A1/A2
SCHEME 9
SCHEME 9
Improved Synthesis of 26
SCHEME 10
SCHEME 10
Retrosynthesis of NP25302
SCHEME 11
SCHEME 11
Feringa's Synthesis of 53 and 54
SCHEME 12
SCHEME 12
Synthesis of trans-2,5-Dimethylproline Ethyl Ester (49)
SCHEME 13
SCHEME 13
Completion of the Synthesis of (±)-NP25302 (12)
FIGURE 3
FIGURE 3
Dihydroquinidine-based catalysts 59 and 60.
SCHEME 14
SCHEME 14
Synthesis of (+)-NP25302
FIGURE 4
FIGURE 4
1H NMR spectral data of Mosher amides 61-64.
SCHEME 15
SCHEME 15
Oxidative Acetoxylation of 26
SCHEME 16
SCHEME 16
Pinto's Synthesis of SB-311009 Analogue 74
SCHEME 17
SCHEME 17
One Step Synthesis of Intermediate 72
None
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References

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    1. For preliminary communication of portions of this work see: Snider BB, Duvall JR, Sattler I, Huang X. Tetrahedron Lett. 2004;45:6725–6727. Snider BB, Duvall JR. Org. Lett. 2005;7:4519–4522.

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    1. For the preparation of analogous compounds with the NH replaced by O or S see: Hamley P, Tinker A. Chem. Abstr. 2000;132:137406a. PCT Int. Appl. WO 00 06,576, 2000.

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