Asymmetric Synthesis of (−)-7-Epiaustraline and (+)-1,7-Diepiaustraline

Abstract

A diastereoselective and modular approach to the synthesis of the 3-hydroxymethyl-2,3,5,6,7,7a-hexahydro-1H-pyrrolizine-1,2,7-triol structure, characteristic of several natural pyrrolizidine natural products has been developed. This approach culminated in the synthesis of (-)-7-epiaustraline and (+)-1,7-diepiaustraline. The oxazolidinone group has been found to be a useful protecting group in the RCM reaction and, as part of a pyrrolo[1,2-c]oxazol-3-one ring system, has functioned as a stereo-and regiodirecting group, in a key diastereoselective cis-dihydroxylation reaction and a regioselective nucleophilic ringopening of a S,S-dioxo-dioxathiole. Abstract: A diastereoselective and modular approach to the synthesis of the 3-hydroxymethyl-2,3,5,6,7,7a-hexahydro-1H-pyrrolizine-1,2,7-triol structure, characteristic of several natural

Synthetic and spectroscopic studies on the structures of uniflorines A and B: structural revision to 1,2,6,7-tetrahydroxy-3-hydroxymethylpyrrolizidine alkaloids

“…10 The amino-alcohol 10 underwent cyclization under Mitsunobu reaction conditions in THF/pyridine as solvent to give the same indolizidine 11 in a modest yield of 25%. 6,18 The use of the Apple cyclization reaction conditions (Ph 3 P/CBr 4 /Et 3 N), 19 that worked well for the cyclization of 1,2-O-dibenzyl-2-epi-9, gave a complex mixture of products. Only the Mitsunobu reaction using pyridine as the solvent gave the desired product.…”

“…1 The proposed structure of uniflorine A is similar to that of castanospermine 2, except for the stereochemistry at C-1 and the extra hydroxyl substitution at C-2. As part of our program concerned with the synthesis of polyhydroxylated indolizidine and pyrrolizidine alkaloids [4][5][6][7][8][9][10][11] we reported an efficient 9-step synthesis of purported uniflorine A from L-xylose. 10 The structure of our synthetic 1 was unequivocally established by a single-crystal X-ray crystallographic study of its pentaacetate derivative.…”

“…Whatever the reasons for the -facial selectivity of 12, this compound and its substituted derivatives have been successfully used by our group, [6][7][8][9]21 and that of Parsons, 23,24 to diastereoselectively prepare polyhydroxylated indolizidine and pyrrolizidine alkaloids and their epimers. When planning our synthesis of 1,2-di-epi-1 we were interested in employing a pyrrolo[1,2-c]oxazin-1-one similar to 14 as a precursor and examining the diastereoselectivity of its DH reactions (Scheme 2).…”

Asymmetric Synthesis of ( - )-Swainsonine

“…Hydrolysis of the oxazolidinone with NaOH in MeOH-water [25] gave the amino alcohol 17 in good yield (84 %). We thought it prudent to protect the secondary alcohol of 17, as it might interfere with the cyclisation of the piperidine ring, by providing an alternative nucleophile to the nitrogen atom.…”

“…4) as more suitable bicyclic substrates to control the DH of substituted pyrrolidines and to simultaneously protect the nitrogen atom from oxidation. [24,25] For example, the unsubstituted pyrrolo[1,2-c]oxazol-3-one 4 underwent DH with catalytic osmium tetraoxide to give exclusively the diol 5 in good yield (Scheme 2). This diol resulted from attack of the oxidizing agent from the concave face of the molecule (Figure 1) due to the pseudo-axial protons H5 and H7a that sterically hinder the -face to attack by the osmium reagent ( Figure 1).…”