Alkaloid Synthesis Paliurine F, Lepadiformine, and 7-Deoxypancratistatin

The Amaryllidaceae alkaloid 7-deoxypancratistatin 21 has potent antiviral activity. A challenge in the assembly of 21 is that the ring fusion is trans, less stable than the corresponding cis diastereomer. The s mthesis of 21 J. Org. Chem. 2007, 72, 2570) by Albert Padwa of Emory University started with 17, the preparation of which by the combination 15 and 16 he had previously reported in the course of his s mthesis of lycoricidine OHL December 11, 2006). Ester 17 had the desired trans ring fusion, but with an angular ester substituent that had to be removed. 

While it would he expected from the mechanism that Rh-mediated decarbonylation of an aldehyde would proceed with retention of absolute configuration, and this had been confirmed experimentally, this reaction had not been pUed to such a challenging substrate. In the event, the transformation proceeded smoothly, to give the desired trans 19. Dehydration and dihydroxylation of 19 led to the cyclic sulfate 20, selective Sj,2 opening of which delivered 7-deoxypancratistatin 21. 

The decarbonylation of 18 was reported on a 2.1 mmol scale, using 3.2 mmol of Wilkinson s catalyst, (Ph3P)3RhCl. For larger scale reactions, it will be important to make this transformation truly catalytic. It has been reported (J. Am. Chem. Soc. 1978,100,7083 J. Org. Chem. 1984, 49, 3195) that inclusion of a bridging ligand such as 1,3-bis-diphe-nylphosphinopropane (dppp) in the decarbonylation can lead to turnover numbers in excess of 100,000. 

In his synthesis of the Dentrobatid alkaloid pumiliotoxin 25 ID 9, Timothy F. Jamison took (J. Org. Chem. 2007, 72, 7451) as his starting material another amino acid, prohne. Ni-mediated cyclization of the epoxide 8 proceeded with high geometric and regiocontrol, to give 9. The chemistry to convert 7 into 8 with high diastereocontrol and without racem-ization is a substantial contribution that wiU have many other applications. 

In his synthesis (Organic Lett. 2007, 9, 2763) of spirotiyprostatin B 12, Barry M. Trost of Stanford University also started with proline, which was readily elaborated to the oxin-dole 10. The question was, could the Pd-catalyzed decarboxylation of 10 be induced to provide specifically 11 Counting geometric isomers of the trisubstituted aUcene, and allylic regioisomers, as well as diastereomers, there were sixteen possible products from this pre-nylation. Using chiral Pd control, the rearrangement proceeded with 14 1 regiocontrol, and 16 1 diasterocontrol. Oxidative cyclization of 11 then delivered spirotiyprostatin B 12. 

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