T. Tsujimoto, Y. Ito / Tetrahedron Letters 48 (2007) 5513–5516
5515
Although configuration of the newly generated stereo-
chemistry of 15/16 seemed to be evident from well-
documented selectivity of the CBS method, rigorous
confirmation was made by synthesizing 16a in an unam-
biguous manner (vide infra).
was identical with the one obtained in a route shown
in Scheme 2.
In conclusion, we established a convergent route to typ-
ical a-GalCers, KRN7000, and OCH, from the common
intermediate 3a. Further investigation to diversify 3a to
synthesize various types of a-GalCer analogues are
under current investigation and will be reported in due
course.
With compounds 16a and 16b, precursors for KRN7000
and OCH, in place, their azide moieties were reduced
with NaBH4 to give corresponding amines. Subsequent
condensation with pentafluorophenyl ester of tetraicosa-
noic or hexaicosanoic acid furnished protected glyco-
sphingolipids 17 (from 16a) and 18 (from 16b),
respectively. Finally, global deprotection by hydrogen-
olysis accomplished the syntheses of KRN7000 (1) and
OCH (2).
Acknowledgments
Financial support from the Japan Society for the Pro-
motion of Science (Grant-in-Aid for Creative Scientific
Research (No. 17GS0420)), the Human Frontier Science
Program, and the RIKEN Ecomolecular Science Pro-
gram are acknowledged. We thank Dr. Masaru Tanigu-
chi for his support and Ms. Akemi Takahashi for her
technical assistance.
To eliminate any uncertainty in the configuration of C-4
hydroxyl groups of sphingosine, we prepared 16a by an
alternative approach (Scheme 4). Starting with com-
pound 19, which was prepared according to the reported
procedure from compound 7,14 desilylation and oxida-
tion of the primary alcohol by Dess–Martin period-
inane15 gave aldehyde 20. Addition of lithium acetylide
gave propargyl alcohols as a mixture of diastereomers
(21a and 21b). After chromatographic separation, they
were converted into D-ribo (22)16 and D-lyxophytos-
phingosine (23)16 by hydrogenation of unsaturated bond
and hydrogenolysis of trityl and benzyl ethers, respec-
tively. Compound 21a, which was correlated with 22,
was then converted to 24. Galactosylation of 24 with
2,3,4,6-tetra-O-benzyl-D-galactopyranosyl acetate (4b)
References and notes
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Scheme 4. Alternative syntheses of intermediate 16 and phytosphingo-
sines. Reagents and conditions: (a) TBAF, THF (95%); (b) Dess–
Martin periodinane, NaHCO3, CH2Cl2 (94%); (c) 1-tetradecyne, BuLi,
THF (97%); (d) H2, Pd/C, EtOH (66%); (e) NaH, BnBr, DMF (90%);
(f) AgClO4, SnCl4, Et2O, CH2Cl2, MS4A (55%).