A. Chen et al. / Tetrahedron Letters 42 (2001) 1251–1254
1253
Scheme 3. Reagents and conditions: i. DMAP, Et3N (50%); ii. MeOH, KCN, DMF, 48 h (88%).
The 17-membered macrocycle 19 contains all the func-
tionality present in the large-ring system of lankacidin
C 1. The conversions that remain to be carried out
include the deprotection of the C(16)-hydroxyl group
with formation of the d-lactone ring, and the introduc-
tion of the N-pyruvyl substituent. As a model study for
this latter transformation, the NH-azetidinone 20 was
acylated on nitrogen using the acid chloride 21 pre-
pared from p-methoxybenzyl protected lactic acid.12
Ring-opening of the N-acylated azetidinone 22 so
obtained using potassium cyanide in methanol N,N-
dimethylformamide gave the N-acylated amino-ester 23
in good yield (Scheme 3).
6. Brain, C. T.; Thomas, E. J., unpublished observations.
7. Duncton, M. A.; Pattenden, G. J. Chem. Soc., Perkin
Trans. 1 1999, 1235–1246.
8. Experimental for 11: Triphenylarsine (7 mg, 23 mmol) was
added to a stirred solution of bis(dibenzylideneace-
tone)palladium (5.3 mg, 5.82 mmol) in a degassed mixture
of anhydrous N,N-dimethylformamide/tetrahydrofuran
(8 cm3; 50:50) at room temperature. A solution of the
azetidinone 10 (18 mg, 19 mmol) in degassed DMF/THF
(4 cm3; 50:50) was added dropwise to the yellow solution
and the resulting dark green solution stirred at room
temperature in the dark for 22 h. Water (5 cm3) and ethyl
acetate (10 cm3) were then added and the aqueous phase
separated and extracted with more ethyl acetate. The
combined organic extracts were washed with brine, dried
(MgSO4) and concentrated under reduced pressure.
Chromatography of the residue using light petroleum/
ethyl acetate (3:2) containing 1% triethylamine as eluent
gave the macrocyclic fused azetidinone 11 (4.4 mg, 52%),
as a white solid [h]D −153 (c 0.43 in CH2Cl2) (found:
M++Na, 544.3071. C28H46O6SiNNa requires M,
544.3070); wmax (cm−1) 3319, 1745, 1621, 1451, 1380, 1249,
1089, 1020, 967, 859 and 835; lH (500 Mz; lankacidin
numbering) (CDCl3) 0.02 [9H, s, Si(CH3)3], 0.88 (2H, m,
SiCH2), 1.09 (3H, d, J 7.5, 17-CH3), 1.26 (3H, s, 2-CH3),
1.69 (3H, s, 11-CH3), 1.72 (3H, s, 5-CH3), 1.74 (1H, m,
15-H), 1.97 (2H, m, 15-H% and 17-H), 2.43–2.61 (2H, m,
9-H2), 2.72 (1H, br. s, OH), 3.37 (1H, br. s, OH),
3.47 (1H, m, OHCHCH2Si), 3.76–3.71 (2H, m, 16-H
Present work is concerned with developing the chem-
istry described in this letter in order to complete a total
synthesis of lankacidin C.
Acknowledgements
We thank the EPSRC and the Thai Government for
support.
References
and OHCHCH2Si), 3.90 (1H, d,
J 2, 18-H), 4.00
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(1H, m, 14-H), 4.33 (1H, m, 8-H), 4.54 (1H, d, J 7,
OHCHO), 4.61 (1H, d, J 10, 3-H), 4.84 (1H, d, J 7,
OHCHO), 5.11 (1H, dd, J 12, 3.5, 10-H), 5.31 (1H, dd, J
15.5, 9.5, 13-H), 5.38 (1H, dd, J 15.5, 9.5, 7-H), 5.48 (1H,
d, J 10, 4-H), 5.81 (1H, s, NH), 6.04 (1H, d, J 15.5, 12-H)
and 6.05 (1H, d, J 15.5, 6-H); m/z (FAB) 544 (M++Na,
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10. The regioselectivity of this monodesilylation contrasted
with the preferred removal of the C(16)-silyl group if the
C(18)-hydroxyl was unprotected (Chen, A.; Thomas, E.
J., unpublished observations).
11. Physical and spectroscopic data for 19: [h]D −131 (c 0.3 in
CH2Cl2) (found: M++Na, 832.4855. C42H75O10NSi2Na
requires M, 832.4827); wmax (cm−1) 3426, 1727, 1498,
1367, 1249, 1166, 1091, 1023, 909 and 836; lH (500 Mz;
lankacidin numbering) (CDCl3) 0.00 [9H, s, Si(CH3)3],
0.09 and 0.12 (each 3H, s, SiCH3), 0.89 (2H, m, SiCH2),
0.90 (3H, d, J 7, 17-CH3), 0.93 [9H, s, SiC(CH3)3], 1.27
(3H, s, 2-CH3), 1.39 [9H, s, OC(CH3)3], 1.57 (2H, m,
15-H2), 1.70 (3H, s, 11-CH3), 1.87 (3H, s, 5-CH3), 2.01