Design and synthesis of macro-heterocycles structurally related to tirofiban

Tetrahedron Letters

Volumn 41, Issue 24, 2000, Pages 4737-4742

  Ramaseshan, Mahesh ^a   Robitaille, Martin ^a   Ellingboe, John W ^b   Dory, Yves L ^a   Deslongchamps, Pierre ^a  

^a Institut de Pharmacologie   (Canada)

^b PFIZER INC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

AMPHOTERICIN; EPOTHILONE A; ERYTHROMYCIN; HETEROCYCLIC COMPOUND; RIFAMPICIN; TIROFIBAN; ZINOSTATIN;

ALKYLATION; ARTICLE; DRUG DESIGN; DRUG STRUCTURE; DRUG SYNTHESIS; ORGANIC CHEMISTRY; REACTION ANALYSIS; SEQUENCE ANALYSIS;

EID: 0034659974     PISSN: 00404039     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0040-4039(00)00709-7     Document Type: Article

References (16)

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7. Tyrosine was treated with tosyl chloride and 1 M NaOH in dioxane, then NaOH in refluxing ethanol to yield Ts-Tyr-OH (57%). Diazomethane treatment in ether gave the corresponding methyl ester quantitatively. The phenol group was protected with DHP and PPTS in dichloromethane (98%) to give 4. Finally the methyl ester was hydrolyzed with 1 M NaOH to yield 27 (99%).
8. Mitsunobu, O. Synthesis 1981, 1.
9. 1,3-Propanediol was monoprotected with DHP and PTSA (96%); the remaining alcohol was oxidized to the aldehyde using Swern conditions (96%). The resulting aldehyde was treated with the anion of triethyl phosphonoacetate to give the corresponding trans acrylate (99%) whose ester was reduced with DIBAH (84%). The resulting alcohol was protected by means of TBDPSCl and imidazole in THF (98%) and the THP ether was cleaved with PPTS in isopropanol at room temperature to give the alcohol 5 (98%).
10. 1,4-Butanediol was monoprotected with DHP and PTSA (73%) to give 8.
11. 1,6-Hexanediol was monoprotected with DHP and PTSA to give 9 (61%).
12. Brillon, D.; Deslongchamps, P. Tetrahedron Lett. 1986, 27, 1131.
13. 3P and 2,6-lutidine in THF to yield the corresponding allylic chloride (87%). The THP ether was cleaved by means of PPTS in dichloromethane and methanol (1:1) to give 22 (91%).
14. 3N in dichloromethane to give the corresponding mesylate quantitatively. The mesylate was transformed into the corresponding iodide by means of NaI in refluxing acetone (90% yield). The iodide was treated with sodium dimethyl malonate in THF to yield the corresponding substituted malonate (98%) whose THP ether was subsequently cleaved with PPTS in dichloromethane and methanol (3:1) to give 25 in 96% yield.
15. 3P and MeI in toluene (84%). Subsequent treatment of that iodide with sodium dimethyl malonate in THF yielded quantitatively the corresponding substituted malonate whose THP ether was cleaved with PPTS in dichloromethane and methanol (3:1) to give 26 in 85% yield.
16. +.