TY - JOUR
T1 - 3-Hydroxyleukotriene B4 (3-OH-LTB4)
T2 - Total Synthesis and Stereochemical Assignment
AU - Bhatt, Rama K.
AU - Chauhan, Kamlesh
AU - Wheelan, Pat
AU - Murphy, Robert C.
AU - Falck, J R
PY - 1994/6/1
Y1 - 1994/6/1
N2 - The asymmetric total synthesis of 3-hydroxyleukotriene B4 (3-OH-LTB4), an ethanol-inducible proinflammatory autacoid, was achieved using a triply convergent strategy for the sequential union of propargylic arsonium salt 3 with pyranosides 2a,b and furanose 4. Both saccharide subunits were derived from commercial 2-deoxy-D-ribose. The key transformation involved palladium-mediated coupling of bromoacetylenide 9 with stannylglycal 6a,b. Subsequent Rieke zinc hydrogenation of acetylene 10a,b and controlled ionic reduction of the cross-conjugated cyclic enol ether using NaBH3CN at pH ~4-4.5 established the cis-Δ6-7-olefin and C(5)-hydroxyl stereochemistry, respectively, and led to 11a,b. Methyllactol hydrolysis, PCC oxidation, methanolysis, and desilylation afforded 3(R)- and 3(S)-OH-LTB4 methyl esters, respectively. On the basis of chromatographic and mass spectral comparisons, enzymatically derived 3-OH-LTB4 is composed principally of the 3(S)-isomer (>95%).
AB - The asymmetric total synthesis of 3-hydroxyleukotriene B4 (3-OH-LTB4), an ethanol-inducible proinflammatory autacoid, was achieved using a triply convergent strategy for the sequential union of propargylic arsonium salt 3 with pyranosides 2a,b and furanose 4. Both saccharide subunits were derived from commercial 2-deoxy-D-ribose. The key transformation involved palladium-mediated coupling of bromoacetylenide 9 with stannylglycal 6a,b. Subsequent Rieke zinc hydrogenation of acetylene 10a,b and controlled ionic reduction of the cross-conjugated cyclic enol ether using NaBH3CN at pH ~4-4.5 established the cis-Δ6-7-olefin and C(5)-hydroxyl stereochemistry, respectively, and led to 11a,b. Methyllactol hydrolysis, PCC oxidation, methanolysis, and desilylation afforded 3(R)- and 3(S)-OH-LTB4 methyl esters, respectively. On the basis of chromatographic and mass spectral comparisons, enzymatically derived 3-OH-LTB4 is composed principally of the 3(S)-isomer (>95%).
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U2 - 10.1021/ja00091a004
DO - 10.1021/ja00091a004
M3 - Article
AN - SCOPUS:0028107980
SN - 0002-7863
VL - 116
SP - 5050
EP - 5056
JO - Journal of the American Chemical Society
JF - Journal of the American Chemical Society
IS - 12
ER -