thetic efforts from a number of laboratories.3,4 Most of the
reported synthetic approaches have utilized simple chiral
building blocks, such as serine and xylose, as the starting
materials. The structurally more related 2 has also served as
a starting material for the synthesis of 1.3e
We recently reported a practical preparative route of
D-erythro-sphingosine synthesis from the low-cost phyto-
sphingosine 2 via the cyclic sulfate intermediate 3 in Figure
2.5 We envisioned that the cyclic sulfate 3 could also serve
demonstrated that the relatively unstrained cyclic sulfate
could permit 5-endo cyclization in preference to 4-exo
cyclization.8d
With these perspectives, we set out to study the transfor-
mation of cyclic sulfate 3 into pachastrissamine (1). Cyclic
sulfate 3 was easily prepared from D-ribo-phytosphingosine
(2) in high overall yield as described in our previous work.5
Because it has been reported that 1-O-silyl-2,3-cyclic sulfate
can be directly converted to 1,2-epoxy-3-sulfate upon depro-
tection of the silyl protecting group,10 we anticipated that
the in situ desilylative cyclization of 3a would lead to the
formation of the desired tetrahydrofuran core. To our delight,
the reaction of cyclic sulfate 3a with n-Bu4NF (TBAF) in
THF at room temperature led, after hydrolysis of the resulting
sulfate ester intermediate 6 with aqueous sulfuric acid, to
the formation of the desired endo-cyclization product 4 as
the only detectable isomer in 86% yield (Scheme 1). No exo-
Scheme 1. Synthesis of Pachastrissamine (1)
Figure 2. Intramolecular opening of cyclic sulfate 3.
as a key intermediate for the synthesis of pachastrissamine
via a 5-endo cyclization. Herein, we wish to report our
studies on this subject.
Cyclic sulfate is like epoxide but much more reactive,6
and many synthetic applications have appeared in the
literature due to its beneficial properties.7 Cyclic sulfates have
been used as intramolecular O-alkylation substrates for the
construction of tetrahydrofuran rings.8 The ring opening of
cyclic sulfate 3 may occur in either a 4-exo-tet or 5-endo-tet
fashion as shown in Figure 2. The 5-endo cyclization would
result in the formation of the desired 2,3,4-trisubstituted
tetrahydrofuran ring system of pachastrissamine. Although
the intramolecular cyclization of tetrahedral systems generally
proceeds via an exo-cyclization pathway,9 Sharpless has
(3) For synthesis of pachastrissamine, see: (a) Ribes, C.; Falomir, E.;
Carda, M.; Marco, J. A. Tetrahedron 2006, 62, 5421-5425. (b) Du, Y.;
Liu, J.; Linhardt, R. J. J. Org. Chem. 2006, 71, 1251-1253. (c) Bhaket, P.;
Morris, K.; Stauffer, C. S.; Datta, A. Org. Lett. 2005, 7, 875-876. (d)
Sudhakar, N.; Kumar, A. R.; Prabhakar, A.; Jagadeesh, B.; Rao, B. V.
Tetrahedron Lett. 2005, 46, 325-327. (e) van den Berg, R. J. B. H. N.;
Boltje, T. J.; Verhagen, C. P.; Litjens, R. E. J. N.; van der Marel, G. A.;
Overkleeft, H. S. J. Org. Chem. 2006, 71, 836-839.
(4) For synthesis of truncated pachastrissamine, see: (a) Chandrasekhar,
S.; Tiwari, B.; Prakash, S. J. ARKIVOC 2006, 155-161. (b) Birk, R.;
Sandhoff, K.; Schmidt, R. R. Liebigs Ann. Chem. 1993, 71-75. (c)
Sugiyama, S.; Honda, M.; Komori, T. Liebigs Ann. Chem. 1990, 1069-
1078. (d) Sugiyama, S.; Honda, M.; Komori, T. Liebigs Ann. Chem. 1988,
619-625.
(5) Kim, S.; Lee, S.; Lee, T.; Ko, H.; Kim, D. J. Org. Chem. 2006, 71,
8661-8664.
(6) Gao, Y.; Sharpless, K. B. J. Am. Chem. Soc. 1988, 110, 7538-7539.
(7) For a review of cyclic sulfates, see: (a) Bonini, C.; Righi, G.
Tetrahedron 2002, 58, 4981-5021. (b) Byun, H.-S.; He, L.; Bittman, R.
Tetrahedron 2000, 56, 7051-7091. (c) Lohray, B. B. Synthesis 1992, 1035-
1052.
1
cyclization product 5 was detected in the crude H NMR
spectra. The relative stereochemistry of 4 was determined
by its conversion to the final natural product 1 as discussed
later.
Alternatively, the trityl ether 3b was able to afford the
same cyclized product 4 as a single isomer (74% yield) by
refluxing in CH3CN with 50 equiv of H2O (Scheme 1). The
free alcohol 4 was isolated directly from the reaction instead
of the sulfate ester intermediate 6, presumably due to the
autocatalytic hydrolysis process in the course of the reac-
tion.11
The azide moiety of 4 was reduced to an amine by
hydrogenation in the presence of Pd/C in MeOH to give a
(8) (a) Defretin, J.; Gleye, C.; Cortes, D.; Franck, X.; Hocquemiller, R.;
Figade`re, B. Lett. Org. Chem. 2004, 1, 316-322. (b) van Delft, F. L.;
Valentijn, A. R. P. M.; van der Marel, G. A.; van Boom, J. H. J. Carbohydr.
Chem. 1999, 18, 191-207. (c) Beauchamp, T. J.; Powers, J. P.; Rychnovsky,
S. D. J. Am. Chem. Soc. 1995, 117, 12873-12874. (d) Kalantar, T. H.;
Sharpless, K. B. Acta Chem. Scand. 1993, 47, 307-313.
(10) Ko, S. Y.; Malik, M.; Dickinson, A. F. J. Org. Chem. 1994, 59,
2570-2576.
(11) The similar cyclization and autocatalytic hydrolysis of sulfate ester
have been described previously. See ref 8c.
(9) Baldwin, J. E. J. Chem. Soc., Chem. Commun. 1976, 734-736.
430
Org. Lett., Vol. 9, No. 3, 2007