Alloyohimbane

This suite of BVMOs is available via whole-cell expression systems and represents a complementary platform of biocatalysts for diverse applications in chiral synthesis. Representatives of this collection were utilized in the enantiodivergent synthesis of the indole alkaloids alloyohimbane and antirhine from a fused bicyclic precursor (Scheme 9.19) [151]. 

A new strategy has been developed for the construction of pentacyclic skeletons of alkaloids such as (-)-alloyohimbane [(-)-365] starting from optically active carbohydrate levoglucosenone (397). 

An elegant one-pot bicycloannulation method for the synthesis of tetrahydroisoquinoline systems has been disclosed by Pawda et al. <1998TL4757, 2000JOC2684>. This method generates a transient thioisomilnchnone 423 that undergoes an intramolecular dipolar cycloaddition. The thus obtained cycloadduct 424 is next reduced with Raney-Ni, followed by LAH to furnish ( )-alloyohimbane 425 in 31% overall yield from 421 (Scheme 109). 

Padwa and co-workers (232,233) adapted their thioisomiinchnone generation-cycloaddition strategy to the synthesis of several tetrahydroisoquinoline alkaloids and the indolo[2,3-a]quinolizidine alkaloid alloyohimbane 333 (Scheme 10.44). 

New synthetic work in the yohimbine series includes syntheses of dimethoxy-hexadehydroyohimbane,68" yohimbane,68 and alloyohimbane.68 68c... 

In a previously described approach, a largely similar strategy was employed in order to generate enantio-selectively (—)-allo-yohimbane [84]. Yohimbane alkaloids such as reserpine and yohimbine were of long-standing interest from pharmacological and synthetic points of view, and the first enantio-selective (—)-alloyohimban synthesis was reported some time ago by Isobe et al. [88]. 

The structure and stereochemistry of this isomer (LXII) have been detailed (Volume VII, p. 58, 70,71). Subsequent work on reserpine, deserpidine, alloyohimbane, and 3-epialloyohimbane completely confirms these assignments (27), but the absolute configuration is not yet certain (28,29). 

The stereochemistry at positions 3,15, and 20 is preserved in alloyo-himbone (LXIV) and its reduction product, alloyohimbane (3a, 15a,20a-yohimbane, LXV), of which several syntheses have been reported (Volume VII, p. 58) (30). In a recent synthesis, tryptamine (XXVI) was condensed with 4-methoxyhomophthalic anhydride (LXVI) to the amide LXVII. This in the five stages shown was converted to LXVIII and the latter, through another series of reactions, converted to LXX consisting of two epimers which were separable. Tosylation of the hydroxyl and ultimate reduction with lithium aluminum hydride generated alloyohimbane (LXV) (31). 

Alternatively, yohimban and alloyohimban were also synthesized via the route of reduction with lithium aluminum hydride of the conjugated lactam (193), followed by catalytic hydrogenation. 

The asymmetric total synthesis of rauwolfia alkaloids (-)-yohimbane and (-)-alloyohimbane was carried out by S.C. Bergmeier et al. by utilizing a novei aziridine-allylsilane cyclization and the Bischler-Napieralski isoquinoline synthesis as key steps.These alkaloids have a characteristic pentacyclic ring framework and exhibit a wide range of interesting biological activities such as antihypertensive and antipsychotic properties. 

JA4879>. A similar approach was used to prepare (—)-alloyohimbane. Photolysis of optically active (24) gave (25) which had previously been converted into the dipeptide sweetener aspartame (26) (Scheme 3) <87TL2595>. 

The Yohimbe alkaloids such as alloyohimbane (1) and the antihypertensive drug reserpine constitute attractive goals for synthetic chemists. Syntheses of Yohimbe alkaloids from noncarbohydrates have been reported. " Synthesis of 1 from cellulose has also been achieved (Scheme 1). Pyrolysis of cellulose gave the levoglucosenone (l,6-anhydro-3,4-dideoxy- 3-D-glycero-hex-3-enopyrano-2-ulose, 2), which underwent Diels-Alder cycloaddition with... 

Isoquinolines are as important as quinolines in the ehemistry of natural produets and there are also many syntheses of these compounds. One of the most important Friedel-Crafts routes is the Bischler-Napieralski reaction.This process is the reaction of an N-acyl amine such as 272 with a reagent sueh as PPA or P2O5 to give an dehydroisoquinoline derivative (273). Wender and Smith used this reaction to convert 274 to 275 in 86% yield as part of a synthesis of yohimhan alkaloids. 167 Shea and co-worker used a similar reaction to synthesize alloyohimbane.l68... 

---