1124
E. Cuny, F. W. Lichtenthaler / Tetrahedron: Asymmetry 17 (2006) 1120–1124
NMe2), 4.26 (m, 1H, 50-H), 5.43 (s, 1H, 10-H), 7.31 (4H-s,
2 BnCH2), 7.4–8.0 (5H-m, Bz-H5). Ms (FD, 25 mA):
m/z = 705 (M++1). Anal. Calcd for C37H40N2O12
(704.74): C, 63.06; H, 5.72. Found: C, 62.90; H, 5.74.
References
1. Martin, D.; Lichtenthaler, F. W. Tetrahedron: Asymmetry
2006, 17, 756–762.
2. Isolation: (a) Mason, D. J.; Dietz, A.; Smith, R. M. Antibiot.
Chemother. 1961, 11, 118–122; Proof of structure: (b) Wiley,
P. F.; Argoudelis, A. D.; Hoeksema, H. J. Am. Chem. Soc.
1963, 85, 2652–2659; Cochran, T. G.; Abraham, D. J.;
Martin, L. L. J. Chem. Soc., Chem. Commun. 1972, 494–495;
for a pertinent review, see: Rosenbrook, W., Jr. J. Antibiot.
1979, 32, S211–S227; Clinical evaluation in gonorrhea: (c)
McCormack, W. M.; Finland, M. Ann. Int. Med. 1976, 84,
712–716; Holloway, W. J. Med. Clin. North Am. 1982, 66,
169–173.
3. (a) Nakajima, M.; Kurihara, N.; Hasegawa, A.; Kurokawa,
T. Liebigs Ann. Chem. 1965, 689, 243–247; (b) Lichtenthaler,
F. W.; Leinert, H.; Suami, T. Chem. Ber. 1967, 100, 2383–
2388; (c) Ogawa, S.; Abe, T.; Sano, H.; Kotera, K.; Suami, T.
Bull. Chem. Soc. Jpn. 1967, 40, 2405–2409; (d) Suami, T.;
Ogawa, S.; Sano, H. Bull. Chem. Soc. Jpn. 1970, 43, 1843–
1846; (e) Schubert, J.; Keller, R.; Schwesinger, R.; Prinzbach,
H. Chem. Ber. 1983, 116, 2524–2545.
4.5. N,N-Bis(benzyloxycarbonyl)-spectinomycin 12
4.5.1. A. De-O-benzoylation of 11. K2CO3 (12 mg) was
added to a methanolic solution of 23 (56 mg, 0.08 mmol,
in 5 mL) and the mixture was stirred for 30 min at room
temperature. Dilution with CH2Cl2 (50 mL), washing with
2 M HCl (20 mL) and water (2 · 20 mL), drying over
Na2SO4 and removal of CH2Cl2 in vacuo left 49 mg
20
(89%) of 12 as a colourless amorphous solid of ½aꢂD
¼
ꢁ4:3 (c 0.9, CHCl3), indistinguishable spectroscopically
1
(IR, H NMR) and chromatographically (CHCl3/MeOH
10:1, n-hexane/EtOAc 5:1, or EtOH) from a sample pre-
pared14 by carbobenzoxylation of commercial (Sigma)
spectinomycin; lit.: [a]D = ꢁ3 (CHCl3),14 ꢁ4.6 (c 0.28,
CHCl3).8
4. Lichtenthaler, F. W.; Lo¨he, A.; Cuny, E. Liebigs Ann. Chem.
1983, 1973–1985.
4.5.2. B. Glycosylation of 10 with actinospectosyl chloride 5,
followed by de-O-benzoylation. Reaction of 10 (320 mg,
1.2 mmol) with 5 (285 mg, 0.6 mmol) in toluene (15 mL)
in the presence of silver alumosilicate13 (360 mg, 1.2 mmol)
5. The alternate possibility, cyclo-hemiketalization of inter-
mediate 6 by OH!C@O attack from the upper (equatorial)
face, would lead to the trans-fused product 8 in which the
axial OBz group is in the less favourable gauche disposition to
the two vicinal ring oxygens.
˚
and molecular sieves 4 A (2 g) for 2.5 h at reflux, followed
by filtration through Kieselgur, evaporation of the filtrate
to dryness in vacuo and exposure of the syrupy residue
of crude 11 to K2CO3 in MeOH for 30 min gave, upon
workup as described under procedure A, crude 12
(Rf = 0.36 in CHCl3/MeOH 9:1) with two minor, slightly
faster spots (ca. 5% each). Purification by HPLC on
Lichrosorb RP-18 (5 lm) with MeOH/water 60:40 at
1 mL/min and removal of the solvents of the appropriate
fraction in vacuo afforded 208 mg of 12 (58%, based on
5) as a colourless solid, identical in all respects with the
product described under A.
6. Lichtenthaler, F. W.; Cuny, E.; Sakanaka, O. Angew. Chem.
2005, 117, 5024–5028; Angew. Chem., Int. Ed. 2005, 44, 4944–
4948.
7. White, D. R.; Birkenmeyer, R. D.; Thomas, R. C.; Mizsak, S.
A.; Wiley, V. H. Tetrahedron Lett. 1979, 2737–2740.
8. Hanessian, S.; Roy, R. J. Am. Chem. Soc. 1979, 101, 5839–
5841; Can. J. Chem. 1985, 63, 163–172.
9. Estimated overall yield as, for example, step 9 of the 23
involved is reported to proceed in a yield of 114%.8
10. A preliminary report on part of this work has appeared.6
11. (a) Ekborg, G.; Garegg, P. J.; Josephson, S. Carbohydr. Res.
1978, 65, 301–306; (b) Evans, M. E.; Parrish, F. W. Methods
Carbohydr. Chem. 1972, 6, 177–179, 193–196; (c) Ref. 4,
footnote 19.
4.6. Spectinomycin 1
12. Suami, T.; Nishiyama, S.; Ishikawa, H.; Okada, H.;
Kinoshita, T. Bull. Chem. Soc. Jpn. 1977, 50, 2754–
2757.
13. (a) van Boeckel, C. A. A.; Beetz, T.; Kock-van Dalen, A. C.;
van Bekkum, H. Recl. Trav. Chim. Pays-Bas 1987, 106, 596–
598; (b) Lichtenthaler, F. W.; Metz, T. Eur. J. Org. Chem.
2003, 3081–3093.
A 100 mg portion of 12 was hydrogenolyzed over 5% Pd/C
(100 mg) in 1:1 iPrOH/water (5 mL) and processed as
described8 to give, upon crystallization from aqueous
acetone, 74 mg (90%) of 1 dihydrochloride pentahydrate
20
as needles with mp 200–204 ꢁC (dec) and ½aꢂD ¼ þ14:3
20
(c 1.1, H2O) {lit. mp 210 ꢁC, ½aꢂD ¼ þ14:0 (c 5, water);16
14. Herrinton, P. M.; Klotz, K. L.; Hartley, W. M. J. Org. Chem.
1993, 58, 678–682.
mp 205–207 ꢁC (dec), [a]D = +14.8 (c 0.42, H2O)8}. IR
1
and H NMR data were identical to the natural product
15. Mitscher, L. A.; Martin, L. L.; Feller, D. R.; Martin, J. R.;
Goldstein, A. W. J. Chem. Soc., Chem. Commun. 1971, 1541–
1542; Hoeksema, H.; Knight, J. C. J. Antibiot. 1975, 28, 240–
241; Strochane, R. M.; Taniguchi, M.; Rinehart, K. L., Jr.
J. Am. Chem. Soc. 1976, 98, 3025–3027; Otsuka, H.;
Mascaretti, O. R.; Hurley, L. H.; Floss, H. G. J. Am. Chem.
Soc. 1980, 102, 6817–6820.
in all respects.
Acknowledgement
We thank the Deutsche Forschungsgemeinschaft and the
Fonds der Chemischen Industrie for support of this work.
16. Sinclair, A. C.; Winfield, A. F. Antimicrob. Agents Chemo-
ther. 1961, 503–506.