Uniflorine

Other reports for the boron-Mannich reaction include the synthesis of aminophenol derivatives,561 a-arylglycines,576 a growth hormone secretagogue NN703,577 a polyhydroxyindolizine alkaloid uniflorine A,578 and cyclic ct-amino acids.579 The reaction has been applied to solution-phase reactions580 and the solid-phase reaction581-585 for the synthesis of libraries of peptides, a-amino acids, and bicyclic diketopiperazines. The reactions were accelerated by the irradiation of microwave.586... 

Trihydroxypipecolic acid (trihydroxylated piperidine) Uniflorine A (= 1,2,6,7,8-Pentahydroxyindolizidine) (indolizidine)... 

Enantioenriched 196 was prepared by ring rearrangement metathesis (RRM) of 197. Through the agency of regio- and stereo-controlled hydroxylation reactions, (+)-castanospermine 198 and both isomers 199 of the pentahydroxylated indolizidine uniflorine-A of putative structure 200 were prepared as shown in Scheme 57 <05T8888>. 

There are no known naturally occurring pentahydroxyindolizidines, although several have been synthesized. Uniflorines A and B from Eugenia uniflora ere. originally formulated as 1,2,6,7,8-pentahydroxyindolizidine (41) and the structurally improbable 5-hydroxylated indolizidine (43), respectively, but these have now been shown to be the polyhydroxypyrrolizidines, 6-f/ /-casuarine and casuarine (39). 

An interesting example starting from L-xylose as the aldehyde component was addressed by Pyne and coworkers for the synthesis of uniflorine A 45 using the PBM reaction and ring-closing metathesis as the key steps (Scheme 4.22) [38]. After the initial PMB step affording intermediate 44, an efficient 8-step synthesis finally rendered uniflorine A 45 [39]. Boronate intermediate 46 was proposed to explain the stereochemical outcome of this reaction, in which the reactive conformation is one that minimized 1,3-ally lie strain as depicted in Scheme 4.22. 

It must be mentioned that the authors corrected the structure of this compound in a later artiele Figure 4.2 [40]. The same group applied this strategy as a key step for the synthesis of other alkaloids such as polyhydroxyindoli-zidine castanospermine 47 [41], the corrected structure of (+)-uniflorine A 48 [40], and the austraUne derivatives 49 and 50 [42]. All these structures are synthesized from a common initial tetrahydroxy amine with the desired configurations. 

T. Ritthiwigrom, A. C. Willis, S. G. Pyne, J. Org. Chem. 2010, 75, 815-824. Total synthesis of uniflorine A, casuarine, aus-traline, 3-epi-australine, and 3,7-di-e/)i-australine from a common precursor. 

Zhao Z, Song L, Mariano PS (2005) A concise sequential photochemical-metathesis approach for the synthesis of (+)-Castanospermine and possible Uniflorine-A stereoisomers. Tetrahedron 61 8888-8894... 

The pyrrolizidine natural products can be obtained by exploitation of the Petasis MCR for combining aldehydes, amines, and vinylboronic acids, as shown by Pyne and coworkers in 2008 [35]. Application of aldopentoses yields polyhydroxylated allyl amines, that provides opportunity for further derivatization to, for example, uniflorines. The MCR commences by boronate-assisted imine formation and protonation (111). Subsequent alkenyl transfer from the borate to the protonated imine delivers the secondary allyl amine 116 in excellent diastereoselectivity (Scheme 14.14). 

The product (112) of D-xylose, allyl amine, and styrylboronic acid was then subjected to a protection/metathesis/dihydroxylation/deprotection/cyclization sequence that produced stereoisomerically pure (-F)-uniflorine A over a total of 11 steps. 

Scheme 14.14 Synthesis of (+)-uniflorine by exploitation of a Petasis MCR sequence. 

Scheme 2.17 Retrosyntheses of (+)-lentiginosine (74) and the putative structure of uniflorine A (75) proceed via similar RCM precursors (76 for 74, 77 for 75).

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