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A Stereoselective and Short Total Synthesis of the Polyhydroxylated γ ‐Amino Acid (−)‐Detoxinine, Based on Stereoselective Preparation of Dihydropyrrole Derivatives from Lithiated Alkoxyallenes
Author(s) -
Flögel Oliver,
Okala Amombo Marlyse Ghislaine,
Reißig HansUlrich,
Zahn Gernot,
Brüdgam Irene,
Hartl Hans
Publication year - 2003
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.200390160
Subject(s) - chemistry , stereoselectivity , imine , enantiopure drug , hydrogenolysis , electrophile , diamino acid , adduct , bicyclic molecule , synthon , total synthesis , stereochemistry , organic chemistry , catalysis , enantioselective synthesis , biochemistry , gene sequence , phylogenetic tree , gene
Based on our earlier results employing lithiated methoxyallene 2 as C 3 building block and imines 3 for the synthesis of dihydropyrrole derivatives 5 , we have investigated chiral imines 6, 10 , and 15 as electrophilic components. Combined with lithiated alkoxyallenes, these imines provide the corresponding primary adducts and finally the dihydropyrrole derivatives 8, 12, 17, 20 , and 22 in good yields and with high to excellent syn selectivities. This stereochemical outcome is interpreted as a result of α ‐chelate control. Treatment with hydrochloric acid converted syn ‐ 8 and syn ‐ 12 into bicyclic compounds 9 and 13 , whereas under more mildly acidic conditions adduct syn ‐ 17 was transformed into diol syn ‐ 18 . The total synthesis of the uncommon γ ‐amino acid (−)‐detoxinine could be achieved by starting from ( S )‐malic acid, which was converted into imine 15 in four steps. Lithiated benzyloxyallene added to imine 15 and efficiently furnished the crucial dihydropyrrole derivative syn ‐ 22 . The hydrogenolysis of this compound did not directly provide the protected triol 29 as anticipated, but a stepwise protocol made the triol available in a fairly satisfactory manner. A second crucial step of the synthesis was the selective oxidation of 29 , which could be achieved by employing platinum dioxide and oxygen. The resulting bicyclic lactone 30 was smoothly transformed into enantiopure (−)‐detoxinine. Thus, a fairly short synthesis of this natural product based on a lithiated alkoxyallene could be performed, demonstrating the potential of these intermediates for syntheses of interesting functionalized heterocyclic compounds.