Leucomycin©
See also “Macrolide Antibiotics” (p. 368)

1. Discovery, producing organism and structures1-10)
Leucomycin was originally isolated from the culture broth of Streptomyces kitasatoensis strain
KA-6T by T. Hata and his co-workers in 19531). Since then, ten components of the antibiotic
complex were isolated by means of silica gel and alumina column chromatographies2).
CHO

CH3
HOO

H3CO

H3C
HOO

OR1CH3N

CH3CH3 OOHO

CH3OR2CH3OO

Streptomyces kitasatoensis KA-6T

Leucomycin A 1
Leucomycin A 3
Leucomycin A 4
Leucomycin A 5Leucomycin A 6
Leucomycin A 7Leucomycin A 8
Leucomycin A 9
Leucomycin U
Leucomycin VR1R2H

COCH2CH(CH3)2

COCH3

COCH2CH(CH3)2

COCH3

COCH2CH2CH3H

COCH2CH2CH3

COCH3H

COCH2CH3
COCH2CH3

COCH3

COCH3HCOCH3

COCH3HHH

The molecular structure of demycarosylleucomycin A3(later corrected to be demycarosyl-iso-leucomycin A3), a hydrolytic product of leucomycin A3, was determined by means of X-ray crystallographic analysis6). The absolute configuration of the lactone ring of leucomycin A3, except
for the chirality of C-9, was established by X-ray analysis. The chirality of C-9 was determinedby allylic rearrangement of the hydroxyl group at C-9 to C-13 during acid hydrolysis6,7). Theabsolute configuration at C-9 was assigned as (S) on the basis of the benzoate or Mill’s rule forleucomycin A3 and its derivatives8). After extensive IR and NMR spectroscopic analysis of leucomycin A3 and 9-epi-leucomycin A39), the absolute configuration at C-9 was reassigned as (R).
In order to resolve these differences and determine the configuration at C-3 as well as those atC-9 and C-17 of 3, 6-bicycloleucomycin A3, a derivative obtained by treatment of leucomycin A3
with lithium hydroxide in ethanol, analysis of diacetyl-3,6-bicycloleucomycinolide A3 by X-ray
crystallography was performed, and the configuration at C-9 was further confirmed to be (R)10).
The total synthesis of leucomycin A3 has been reported by two groups. The first total synthesis
was reported by Tatsuta et al.11) (See Appendix-I).

CHO

CH3O

H3COH3CHOONCH3CH3 OHCH3H3COCOHH

OCOCH3H3COHOCOCH3
CH3HOCHOCH3OOOO

Demycarosylleucomycin A 3(Demycarosyl-iso-leucomycin A 3)

Diacetyl-3,6-bicycloleucomycin A 3

2. Physical data (Leucomycin A3)2)
White powder. C42H69NO15; mol wt 785.46. Sol. in CHCl3, EtOH, dioxane, EtOAc, acetone. Easily crystallized from benzene.
3. Biological activity12,13)
1) Antimicrobial activity12)
Test organism
Staphylococcus aureus
Leucomycin A1
Leucomycin A3
Leucomycin A4
Leucomycin A5
Leucomycin A6
Leucomycin A7
Leucomycin A8
Leucomycin A9
Leucomycin ULeucomycin V

0.04
0.04
0.15
0.80
0.04
0.15
0.60
0.30
3.12
3.12

MIC (µg/ml)

Bacillus subtilis Klebsiella pneumoniae
0.60
0.60
1.25
0.30
0.60
0.30
2.50
1.25
6.25
—10101051010101025252) Leucomycin A3 showed effective action against influenza A virus infection in vivo.13)
3. Leucomycin is commercially available as antibacterial medicine.
4. References
1.		
T. Hata et al., J. Antibiot. 6, 87-89 (1953)
2. [25] S. Ōmura et al., J. Antibiot. 21, 532-538 (1968)
3. [13] S. Ōmura et al., Tetrahedron Lett. 1267-1271 (1967)
4. [23] S. Ōmura et al., J. Antibiot. 21, 272-278 (1968)
5. [53] S. Ōmura et al., Tetrahedron 28, 2839-2848 (1972)
6. [31] M. Hiramatsu et al., Bull. Chem. Soc., Jpn. 43, 1966-1975 (1970)
7. [33] S. Ōmura et al., Chem. Pharm. Bull. 18, 1501-1508 (1970)
8. [75] S. Ōmura et al., J. Antibiot. 27, 370-372 (1974)
9.		
L. A. Freiberg et al., J. Org. Chem. 39, 2474-2476 (1974)
10. [121] A. Ducruix et al., J. Chem. Soc., Chem. Commun. 1976, 947-948 (1976)
11.		
K. Tatsuta et al., Tetrahedron Lett. 21, 2837-2840 (1980)
12. [30] S. Ōmura et al., In “Proceedings of the 6th International Congress of 					Chemotherapy” pp.1043-1049, University of Tokyo Press (1970)
13. [1162] R. Sugamata et al., J. Antibiot. 67, 213-222 (2014)