(-)-borrelidin

Names

[ Name ]:
(-)-borrelidin

[Synonym ]:
Borrelidin
Cyclopentanecarboxylic acid, 2-[(2S,4Z,6Z,8R,9S,11R,13S,15S,16S)-7-cyano-8,16-dihydroxy-9,11,13,15-tetramethyl-18-oxooxacyclooctadeca-4,6-dien-2-yl]-, (1R,2R)-
Borrelidine
Quinquangulin K 031
2-(7-CYANO-8,16-DIHYDROXY-9,11,13,15-TETRAMETHYL-18-OXOOXACYCLOOCTADECA-4,6-DIEN-2-YL)-CYCLOPENTANECARBOXYLIC ACID
Quinquangulin K 182
Cyclopentanecarboxylic acid, 2-[(2S,4E,6Z,8R,9S,11R,13S,15S,16S)-7-cyano-8,16-dihydroxy-9,11,13,15-tetramethyl-18-oxooxacyclooctadeca-4,6-dien-2-yl]-, (1R,2R)-
(1R,2R)-2-[(2S,4Z,6Z,8R,9S,11R,13S,15S,16S)-7-Cyano-8,16-dihydroxy-9,11,13,15-tetramethyl-18-oxooxacyclooctadeca-4,6-dien-2-yl]cyclopentanecarboxylic acid
(1R,2R)-2-[(2S,4E,6Z,8R,9S,11R,13S,15S,16S)-7-Cyano-8,16-dihydroxy-9,11,13,15-tetramethyl-18-oxooxacyclooctadeca-4,6-dien-2-yl]cyclopentanecarboxylic acid
(-)-borrelidine
TREPONEMYCIN

Biological Activity

[Description]:

Borrelidin (Treponemycin) is a nitrile-containing macrolide antibiotic isolated from Streptomyces rochei, which acts as an inhibitor of bacterial and eukaryal threonyl-tRNA synthetase, can target ALL cell lines by inducing apoptosis and mediating G(1) arrest. Borrelidin (Treponemycin) is an inhibitor of a cyclin-dependent kinase (CDK) of the budding yeast, Cdc28/Cln2 with an IC50 of 24 μM. Borrelidin (Treponemycin) is a potent angiogenesis inhibitor with an IC50 of 0.8 nM for capillary tube formation, and induces apoptosis of the tube-forming cells. Borrelidin (Treponemycin) has strong antimalarial activities, with IC50s of 1.9 nM and 1.8 nM against K1 and FCR3 strains of Plasmodium falciparum[1][2][3].

[Related Catalog]:

Signaling Pathways >> Anti-infection >> Parasite

Signaling Pathways >> Apoptosis >> Apoptosis

Research Areas >> Infection

Signaling Pathways >> Cell Cycle/DNA Damage >> CDK

[Target]

IC50：24μM (Cdc28/Cln2)[2]

[References]

[1]. Habibi D, et al. Borrelidin, a small molecule nitrile-containing macrolide inhibitor of threonyl-tRNA synthetase, is a potent inducer of apoptosis in acute lymphoblastic leukemia. Invest New Drugs. 2012 Aug;30(4):1361-70.

[2]. Tsuchiya E, et al. Borrelidin inhibits a cyclin-dependent kinase (CDK), Cdc28/Cln2, of Saccharomyces cerevisiae. J Antibiot (Tokyo). 2001 Jan;54(1):84-90.

[3]. Wakabayashi T, et al. Borrelidin is an angiogenesis inhibitor; disruption of angiogenic capillary vessels in a rat aorta matrix culture model. J Antibiot (Tokyo). 1997 Aug;50(8):671-6.

[4]. Otoguro K, et al. In vitro and in vivo antimalarial activities of a non-glycosidic 18-membered macrolide antibiotic, borrelidin, against drug-resistant strains of Plasmodia. J Antibiot (Tokyo). 2003 Aug;56(8):727-9.

Chemical & Physical Properties

[ Density]:
1.1±0.1 g/cm3

[ Boiling Point ]:
710.3±60.0 °C at 760 mmHg

[ Melting Point ]:
143-145℃

[ Molecular Formula ]:
C₂₈H₄₃NO₆

[ Molecular Weight ]:
489.644

[ Flash Point ]:
383.4±32.9 °C

[ Exact Mass ]:
489.309052

[ PSA ]:
127.85000

[ LogP ]:
4.31

[ Vapour Pressure ]:
0.0±5.1 mmHg at 25°C

[ Index of Refraction ]:
1.539

[ Water Solubility ]:
DMSO: 1 mg/mL

Toxicological Information

CHEMICAL IDENTIFICATION

RTECS NUMBER :: ED8750000

CHEMICAL NAME :: Borrelidin

CAS REGISTRY NUMBER :: 7184-60-3

BEILSTEIN REFERENCE NO. :: 0066270

LAST UPDATED :: 199612

DATA ITEMS CITED :: 5

MOLECULAR FORMULA :: C28-H43-N-O6

MOLECULAR WEIGHT :: 489.72

WISWESSER LINE NOTATION :: T-18-OV MU OUTJ DQ E1 G1 I1 K1 LQ MCN R- AL5TJ BVQ

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Subcutaneous

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 1780 ug/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

REFERENCE :: JCINAO Journal of Clinical Investigation. (Rockefeller Univ. Press, 1230 York Ave., New York, NY 10021) V.1- 1924- Volume(issue)/page/year: 28,1047,1949

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 2 mg/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

REFERENCE :: 85ERAY "Antibiotics: Origin, Nature, and Properties," Korzyoski, T., et al., eds., Washington, DC, American Soc. for Microbiology, 1978 Volume(issue)/page/year: 2,1198,1978

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Subcutaneous

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 75 mg/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

REFERENCE :: JCINAO Journal of Clinical Investigation. (Rockefeller Univ. Press, 1230 York Ave., New York, NY 10021) V.1- 1924- Volume(issue)/page/year: 28,1047,1949

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 39 mg/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

REFERENCE :: JCINAO Journal of Clinical Investigation. (Rockefeller Univ. Press, 1230 York Ave., New York, NY 10021) V.1- 1924- Volume(issue)/page/year: 28,1047,1949

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Intramuscular

SPECIES OBSERVED :: Bird - chicken

DOSE/DURATION :: 74 mg/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

REFERENCE :: 85ERAY "Antibiotics: Origin, Nature, and Properties," Korzyoski, T., et al., eds., Washington, DC, American Soc. for Microbiology, 1978 Volume(issue)/page/year: 2,1198,1978

Safety Information

[ Personal Protective Equipment ]:
Eyeshields;Gloves;type N95 (US);type P1 (EN143) respirator filter

[ Hazard Codes ]:
T+

[ Safety Phrases ]:
24/25

[ RIDADR ]:
NONH for all modes of transport

[ WGK Germany ]:
3

[ RTECS ]:
ED8750000

[ HS Code ]:
29419090

Synthetic Route

Click to get detail synthetic route

Articles

Further characterization of Bacillus subtilis antibiotic biosensors and their use for antibacterial mode-of-action studies.

Antimicrob. Agents Chemother. 55(4) , 1784-6, (2011)

We further examined the usefulness of previously reported Bacillus subtilis biosensors for antibacterial mode-of-action studies. The biosensors could not detect the tRNA synthetase inhibitors mupiroci...

Total synthesis of borrelidin.

J. Org. Chem. 72 , 2744, (2007)

The total synthesis of borrelidin has been achieved. The best feature of our synthetic route is macrocyclization at C11-C12 for the construction of an 18-membered ring after esterification between two...

Iterative deoxypropionate synthesis based on a copper-mediated directed allylic substitution: formal total synthesis of borrelidin (C3-C11 fragment).

Chemistry 12(25) , 6684-91, (2006)

A new iterative strategy for the flexible preparation of any oligodeoxypropionate stereoisomer is presented which relies on an o-DPPB-directed copper mediated allylic substitution employing enantiomer...