4742
4. Egbertson, M.; Chang, C. T.-C.; Duggan, M. E.; Gould, R. J.; Halczenko, W.; Hartman, G. D.; Laswell, W. L.;
Lynch Jr, J. J.; Lynch, R. J.; Manno, P. D.; Naylor, A. M.; Prugh, J. D.; Ramjit, D. R.; Sitko, G. R.; Smith, R. S.;
Turchi, L. M.; Zhang, G. J. Med. Chem. 1994, 37, 2537.
5. Ndibwami, A.; Lamothe, S.; Guay, D.; Plante, R.; Soucy, P.; Golstein, S. Deslongchamps, P. Can. J. Chem. 1993,
71, 695.
6. Tyrosine was treated with tosyl chloride and 1 M NaOH in dioxane, then NaOH in re¯uxing 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%).
7. Mitsunobu, O. Synthesis 1981, 1.
8. 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%).
9. 1,4-Butanediol was monoprotected with DHP and PTSA (73%) to give 8.
10. 1,6-Hexanediol was monoprotected with DHP and PTSA to give 9 (61%).
11. Brillon, D.; Deslongchamps, P. Tetrahedron Lett. 1986, 27, 1131.
12. The allylic alcohol obtained after DIBAH reduction (see Ref 8) was treated with hexachloroacetone, Ph3P 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%).
13. The alcohol 8 was treated with MsCl and Et3N in dichloromethane to give the corresponding mesylate
quantitatively. The mesylate was transformed into the corresponding iodide by means of NaI in re¯uxing
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.
14. The alcohol 9 was transformed into the corresponding iodide with DEAD, Ph3P 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.
1
15. Macrocycle 3 analytical data: H NMR (CDCl3): ꢀ 1.03 (m, 2H), 1.25 (m, 2H), 1.42 (m, 2H), 1.65 (m, 4H), 2.43
(bs, 3H), 2.51 (m, 4H), 2.92 (m, 1H), 3.25 (m, 3H), 3.63 (s, 3H), 3.68 (s, 3H), 4.07 (t, 3H, J=6.2 Hz), 4.32 (m, 1H),
4.85 (m, 1H), 4.94 (m, 1H), 6.78 (d, 2H, J=8.79 Hz), 7.06 (d, 2H, J=8.51 Hz), 7.27 (m, 2H), 7.74 (d, 2H, J=8.24
Hz). 13C NMR (CDCl3): ꢀ 21.92, 23.23, 24.93, 28.52, 28.69, 31.30, 35.29, 36.66, 48.94, 52.55, 52.70, 57.26, 63.13,
67.38, 115.23, 125.99, 127.91, 128.95, 129.58, 130.53, 131.02, 171.20, 171.88. MS (EI, 70 eV): 630 [M+H]+.