Synthesis of (−)-7-Epiaustraline and (−)-1-Epicastanospermine

Abstract

Highly efficient and selective syntheses of the title compounds are described. The cornerstone of the synthetic plan is the tandem inter [4 + 2]/inter [3 + 2] cycloaddition process. These syntheses differ from previous applications of this strategy in that they incorporate an alkylation in the hydrogenolysis step to close the second ring of the azabicyclic systems. Notable features of the sequence are (1) the highly regio- and stereoselective [3 + 2] cycloaddition of nitronate 15 with siloxymethyl (Z)-beta-silylvinyl ketone (Z)-22b and (2) the highly selective reduction of the resulting ketone 24a with L-Selectride. A single-crystal X-ray structure analysis of synthetic (-)-7-epiaustraline confirmed that the targeted structure was successfully synthesized. This stimulated a reexamination of the structural assignment of the natural product. (-)-1-Epicastanospermine was synthesized in four steps from the common intermediate 27a. The absolute configuration of (-)-1-epicastanospermine was assured by single-crystal X-ray structure analysis of intermediate (-)-27a. Thus, the sign of the optical rotation had to be revised. The overall efficiency of these syntheses were 9 steps and 23% yield for (-)-7-epiaustraline and 10 steps and 20% yield for (-)-1-epicastanospermine

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

“…[ 6,4.5 Hz),3.55 (dd,1H,J 4.2,9.6 Hz),3.47 (dd,1H,J 5.7,9.9 Hz),3.29 (ddd,1H,J 6.6,6.9,10.8 Hz),3.04 (ddd,1H,J 4.2,5.7,9.6 Hz),2.89 (ddd,1H,J 6.3,6.6,10.  7.95 (dd,2H,J 1.2,8.4 Hz),1H),2H),5H),7.21 (d,2H,J 8.7 Hz),6.84 (d,2H,J 8.7 Hz),5.16 (dd,1H,J 4.8,7.8 Hz),4.98 (ddd,1H,J 3.9,7.8,11.7 Hz),1H),4.61 (d,1H,J 12.0 Hz), 4.54 (d,1H,J 12.6 Hz),4.42 (d,1H,J 11.4 Hz),4.37 (d,1H,J 11.4 Hz),…”

Stereoselective synthesis and stereochemistry of seven isomeric spiroacetal structures based on the C17–C28 fragment (CD rings) of spongistatin 1

“…15 The product was purified by flash chromatography (silica; 30% EtOAc in hexane) to provide the required aldehyde 6, (9.5 g, 93% …”

Nitroalkenes as Amination Tools

“…Trialkylsilyl substituents are known to undergo Tamao -Fleming oxidation, thus acting as surrogates for hydroxy groups in several synthetic processes. Five of the six stereocenters required for the synthesis of the pyrrolizidine alkaloids (+) -7 -epiaustraline [100,101] and (+) -causarine [102,103] are created in a tandem [4+2]/[3+2] cycloaddition involving nitroalkene 101 , a chiral enol ether, and a ( Z ) -vinylsilane 102 (TDSO = dimethylthexylsilyloxy) (Scheme 3.53 ).…”