6.7- Secoagroclavine

After discovery of the tungstate method, we examined its applicability to the preparation of 317. As usual, ( )-6,7-secoagroclavine (319) is reduced with NaBH3CN in a mixture of TFA and AcOH to the 2,3-dihydro derivative 320. Although the products are separated to a major (72%) and a minor diastereoiso-mer (16%), determination of their stereochemistries is not complete. Applications of the tungstate method to each isomer afford the same product, 1-hydroxy-6,7-secoagrocalvine (321). However, 321 is not stable enough to characterize. 

Synthesis of the 1-methoxy analogue of ( )-6,7-secoagroclavine 226 and its des-methyl derivative (227) have been developed from 2-nitrotoluene, proceeding through 1-methoxyindole in nine steps with an overall yield of 20% (86CPB677). 

Independently, Somei et a/.34 have reported three syntheses of ( )-6,7-secoagroclavine (42), each of which starts with the unsaturated indole-ketone (49), itself prepared in three stages from 5-nitroisoquinoline. The shortest of these syntheses is outlined in Scheme 7. 

However, the most important of Somei s contributions in this area are Heck reactions of haloindoles with allylic alcohols [26, 248a,c-f,h,i]. For example, reaction of 4-iodo-3-indolecarboxaldehyde with 2-methyl-3-buten-2-ol afforded alcohol 231 in high yield. This could be subsequently transformed to ( )-6,7-secoagroclavine (232) [248c]. Interestingly, the one-pot thallation-palladation protocol failed in this case. 

An alternative synthesis constitutes yet another synthesis of ( )-6,7-secoagroclavine... 

Secoagroclavine Synthesis of the versatile intermediate 4-(sulfonyl-methyl)indole from 4-oxo-4,5,6,7-tetrahydioindole for the formal total synthesis [28]... 

Horwell, D.C. and Verge, J.P. (1979) Isolation and identification of 6, 7-secoagroclavine from Claviceps purpurea. Phytochemistry, 18, 519. 

B. epichloe clianoclavine-l, isochano-cla ine-I, agroclavine, elymoclavine, penniclavine, ergonovine, ergonovinine, 6,7-secoagroclavine Bacon et al. (1979) Porter et al. (1979) Porter et al. (1981)... 

Synthesis of 6,7-Secoagroclavines, Chanoclmine /, Isochmoclavine /, Norchanocla/ine I, Chanoclavine II, Norchanoclavine //, and Their Enantiomers... 

Optical resolution of the key intermediates, trans 41 and cis 4 2, was achieved, with base-line resolution, by chiral column chromatography on a chindpak AS column, to afford (-)-trans 41, (+)-inns 41, (-)-cis 42, and (+)-c 42 on a semi-preparative scale. The first total syntheses of (-)-6,7-secoagroclavine 47] and its (+>enantionier [(+)-/ranr 4 7] were completed in a one-pot operation by the reaction of (-)- and (+)-trans 41 with an excess of methylmagnesium iodide, respectively, followed by reduction of the resulting methylhydroxykunines [(-)- and (+)-tnms 49], with zinc in metiianolk hydrochloric acid. 

Somei et d. also disclosed that ( )-6-nor-6-propyl-6,7-secoagroclavine [( )-7 2, KSU 1415] showed potent dopamine agonistic activity (50). 

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