Bone collagen cross-links: a convergent synthesis of (+)-deoxypyrrololine.
A convergent total synthesis of (+)-deoxypyrrololine (Dpl, 4), a putative cross-link of bone collagen, is described starting from a commercially available L-glutamic acid derivative, (4S)-5-(tert-butoxy)-4-[(tert-butoxycarbonyl)amino]-5- oxopentanoic acid (16). Condensation of aldehyde (S)-(-)-17 with nitro compound (S)-(-)-27, both of which were prepared from a common precursor (S)-16, gave the alpha-hydroxynitro compound 28, which upon acetylation afforded alpha-acetoxynitro compound 14 in good yield. Subsequent condensation and cyclization of alpha-acetoxynitro compound 14 with benzyl isocyanoacetate (15) in the presence of DBU in THF gave the key pyrrole intermediate (S,S)-(-)-12 in 57% yield. N-Alkylation of pyrrole (S,S)-(-)-12 with iodide (S)-(-)-13 using t-BuOK in THF afforded the 2-benzyloxycarbonyl-1,3,4-substituted pyrrole derivative (-)-29 in 42% yield. Removal of the protective groups in (-)-29 followed by hydrogenolysis and decarboxylation afforded the cross-link (+)-Dpl (4) in good overall yield. The synthesis of an analogue (S)-(+)-24 and formation of a novel tetrahydroindole derivative (-)-31 are also described.
Adamczyk
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Department of Chemistry (9NM, Bldg AP20), Diagnostics Division, Abbott Laboratories, 100 Abbott Park Road, Abbott Park, Illinois 60064-6016, USA. maciej.adamczyk@abbott.com
Johnson
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Reddy
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D000596:Amino Acids / Q000138:chemical synthesis / Q000737:chemistry*; D001842:Bone and Bones / Q000737:chemistry*; D002851:Chromatography, High Pressure Liquid; D003094:Collagen / Q000737:chemistry*; D003432:Cross-Linking Reagents / Q000138:chemical synthesis / Q000737:chemistry; D007093:Imidazoles / Q000138:chemical synthesis / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D021241:Spectrometry, Mass, Electrospray Ionization
D000596:Amino Acids; D003432:Cross-Linking Reagents; D007093:Imidazoles; C405607:deoxypyrrololine; D003094:Collagen