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. Author manuscript; available in PMC: 2013 Oct 17.
Published in final edited form as: J Am Chem Soc. 2012 Oct 4;134(41):17320–17332. doi: 10.1021/ja308429f

Scheme 6.

Scheme 6

Synthesis of Dithiodiketopiperazines 46 and 2,2′-epi-46, and bis-(Methylthio)diketopiperazines 55 and 2,2′-epi-55a and Stereochemical Assignments of 55 and 2,2′-epi-55 by NOESY Studies (Arrows Designate NOESY Correlations)

aReagents and conditions. a) NaHMDS (0.6 M in PhMe, 3.0 equiv), S8 (1.0 equiv), THF, 25 °C, 1 min; then 45 (1 M in THF, 1.0 equiv), 1 min; then NaHMDS (0.6 M in PhMe, 2.0 equiv), 25 °C, 30 min; b) NaBH4 (25 equiv), THF/MeOH (1:1), 0→25 °C, 45 min; then MeI (50 equiv), 25 °C, 15 h, 58% over the three steps from 45 (55:2,2′-epi-55 ca. 1.4:1 dr); c) NaBH4 (25 equiv), THF/MeOH (1:1), 0→25 °C, 0.75 h; then KI3 aq. (1.4 M), 25 °C, 10 min, 55% over the three steps from 45 (46: 2,2′-epi-46 ca. 1.4:1 dr); d) NaBH4 (25 equiv), THF/MeOH (1:1), 0→25 °C, 45 min; then MeI (50 equiv), 25 °C, 15 h, 65% from 46(55:2,2′-epi-55 ca. 1.4:1 dr).