A biomimetic approach for bicyclic alkaloids using acetal pro-nucleophile: total synthesis of (±)-epilupinine and formal syntheses of (±)-laburnine, (±)-isoretronecanol, (±)-tashiromine

Glycal approach to the synthesis of macrolide (−)-A26771B

“…Its deacetylation with 5 sodium methoxide in MeOH followed by regioselective protection of the resulting primary OH group with tbutylchlorodiphenyl silane (TBDPSCl) and imidazole furnished compound 12 in 92% yield. Its Wittig olefination with methyltriphenylphosphonium bromide in the presence 10 of t-BuOK produced the unsaturated alcohol 13 in 60% yield. However, its yield was increased to 81% when n-BuLi was used in place of t-BuOK.…”

“…To this solution, DMSO (0.68 ml, 9.66 mmol) was added drop wise and the stirring was continued for 5 min. The alcohol 14 (600 mg, 3.22 mmol) dissolved in DCM was 10 added drop wise to the above reaction mixture and the stirring was further continued for 30 min at the same temperature. Afterward, Et3N (2.25 ml, 16.1 mmol) was now added drop wise to it and the stirring was continued till the completion of the reaction.…”

“…5 (-)-A26771B (1): A solution of above macrolide 2 (15 mg, 0.053 mmol), succinic anhydride (10.6 mg, 0.106 mmol), and DMAP (12.7 mg, 0.106 mmol) in CH2Cl2 (3 mL) was stirred for 24 h at room temperature. Evaporation of the solvent followed by the purification of the crude product 10 by flash chromatography (SiO2; 5% MeOH/CH2Cl2) afforded 10 mg (72%) of the title macrolide 1 as a white solid: [α]D 26 -12.4 (c 0.05, MeOH); Rf. 0.21 (5% MeOH/CH2Cl2); IR (Neat): νmax 3150, 3019, 2938, 2855, 1742, 1703, 1381, 1300, 1196, 11581 H (400 Inanaga, K. Hirata, H. Saeki, T. Katsuki, M. Yamaguchi, Bull.…”

Synthetic Strategies towards the Azabicyclo[3.3.0]-Octane Core of Natural Pyrrolizidine Alkaloids. An Overview

“…The initially presented synthesis used Broensted acid (p-toluenesulfonic acid) as a catalyst (86% yield). 211 A specifically substituted hydroxylactam served as the appropriate starting material in the Mannich cyclization process. Reduction with NaBH 4 in situ resulted in the formation of the diastereomeric pyrrolizidines, which could be then converted to the final PAs isoretronecanol and laburnine.…”

Regio and diastereoselective multicomponent 1,3-dipolar cycloadditions between prolinate hydrochlorides, aldehydes and dipolarophiles for the direct synthesis of pyrrolizidines

“…2 The synthesis of all these alkaloids is not so simple, for example, (+)-2 and (+)-5, have been prepared by diastereoselective [4+2] cycloadditions using nitroalkenes and a chiral vinyl ether, 4a,b and by diastereoselective [2+2] dichloroketene-chiral enol ether cycloaddition, 6 respectively. Besides, (-)-8 to (-)-10 scaffolds were prepared by double M A N U S C R I P T 7 or through a biomimetic Mannich-type reaction, 8 or by metathesis. 9 In order to facilitate their synthesis, several diastereoselective approaches to these heterocyclic frameworks have been successfully attempted.…”