65195-55-3 Usage
Description
Avermectin B1a is a macrocyclic lactone disaccharide anthelmintic agent that binds to high and low affinity sites on the mammalian GABAA receptor. Binding to the high affinity site activates the receptor to increase chloride influx, while binding to the low affinity site blocks the channel. Avermectin B1a inhibits binding of the glycine receptor antagonist strychnine to membranes and the solubilized receptor from rat spinal cord (Kis = 1.3 and 3.6 μM, respectively). Formulations containing avermectin B1a (>80%) and avermectin B1b (~20%; ) are used in insecticides and veterinary anthelmintic formulas as abamectin .
Originator
Abamectin,Yellow River
Enterprise Co. (a.k.a
Yelori)
Uses
Avermectin B1a is the major component (>80%) of a commercially available anthelmintic used to control parasitic nematodes in livestock. Avermectin B1a contains a secbutyl residue in the 25-position. In vitro and in vivo studies have shown that this analogue is the more potent analogue in the commercial product.
Manufacturing Process
1. The contents of a lyophilized tube of Streptomyces avermitilis MA-4680 is
transferred aseptically to a 250 ml Erlenmeyer flask containing 305 ml of
Medium 1: Dextrose 20 g, Peptone 5 g, Meat Extract 5 g, Primary Yeast 3 g,
NaCl 5 g, CaCO3 (after pH adjustment) 3 g, Distilled water 1000 ml, pH 7.0.
The inoculated flask is incubated for 3 days at 28°C on a rotary shaking
machine at a speed of 220 RPM in a 2 inch radius circular orbit. At the end of
this time, a 250 ml Erlenmeyer flask containing 50 ml of Medium 2 [Tomato
Paste 20 g, Modified Starch (CPC) 20 g, Primary Yeast 10 g, CoCl2·6H2O 0.005
g, Distilled water 1000 ml, pH 7.2-7.4] is inoculated with a 2 ml sample from
the first flask. This flask is incubated for 3 days at 28°C on a rotary shaking
machine at a speed of 220 RPM in a 2 inch diameter circular orbit. 50 Ml of
the resulting fermentation broth containing C-076 is effective against an
N.dubius infection in mice.2. A lyophilized tube of Streptomyces avermitilis MA-4680 is opened
aseptically and the contents suspended in 50 ml of Medium 1 in a 250 ml
Erlenmeyer flask. This flask is shaken for 3 days at 28°C on a rotary shaking
machine 220 RPM with a 2 inch diameter circular orbit. A 0.2 ml portion of
this seed medium is used to inoculate a Slant of Medium 3: Dextrose 10.0 g ,
Bacto Asparagine 0.5 g, K2HPO4 40.5 g, Bacto Agar 15.0 g , Distilled water
1000 ml, pH 7.0. The inoculated slant medium is incubated at 28°C for 10
days and stored at 4°C until used to inoculate 4 more slants of Medium 3.
These slants are incubated in the dark for 8 days. One of these slants is used
to inoculate 3 baffled 250 ml Erlenmeyer flasks containing 50 ml of No. 4
Seed Medium: Soluble Starch 10.0 g, Ardamine 5.0 g, NZ Amine E 5.0 g, Beef
Extract 3.0 g, MgSO4·7H2O 0.5 g, Cerelose 1.0 g, Na2HPO4 0.190 g, KH2PO4
182 g, CaCO3 0.5 g, Distilled water 1000 ml, pH 7.0-7.2. The seed flasks are
shaken for 2 days at 27-28°C on a rotary shaking machine at 220 RPM with a
2 inch diameter circular orbit. The contents of these flasks are pooled and
used to inoculate (5% inoculum) baffled 250 ml Erlenmeyer flasks containing
40 ml of various production media. Flasks containing media 2, 5 and 6 are
incubated for 4 days at 28°C on a rotary shaking machine at 220 RPM with a
2 inch diameter circular orbit. The resulting broth containing C-076 is then
harvested and tested for anthelmintic activity. In all cases 6.2 ml of whole
broth and the solids obtained from centrifuging 25 ml of whole broth are fully
active against N.dubius helminth infections in mice.3. The one of the four slants of Medium 3 prepared as in Example 2 is used to
inoculate a baffled 250 ml Erlenmeyer flask containing 50 ml of Seed Medium
No. 4. The seed flask is shaken for 1 day at 27- 28°C on a rotary shaking
machine at 220 RPM with a 2 inch diameter circular orbit. The seed flask is
then stored stationary at 4°C until it is ready to be used. The contents of this
flask are then used to inoculate (5% inoculum) 20 unbaffled 250 ml
Erlenmeyer flasks containing 40 ml of Medium No. 2. After 4 days incubation
at 28°C on a rotary shaking machine at 220 RPM with a 2 inch diameter
circular orbit, 19 of the flasks are harvested and pooled. The combined
fermentation broths
containing C-076 are filtered affording 500 ml of filtrate and 84 g of mycelia.
78 G of mycelia are extracted with 150 ml of acetone for ? hour with stirring
and the mixture filtered. The filter cake is washed with 50 ml of acetone and
the filtrate and washings are combined and concentrated to 46.5 ml 30 Ml of
the concentrate is adjusted to pH 4 with dilute hydrochloric acid and extracted
3 times with 30 ml portions of chloroform. The extracts are dried by filtering
through dry Infusorial Earth (Super-Cel) combined and concentrated to
dryness in vacuum. The oily residue of C-076 weighing 91.4 mg is dissolved in
chloroform sufficient to make 3 ml of solution which represents 1% of broth
volume. The C-076 (Abamectin) obtained in this recovery procedure is fully
active against N.dubius infections in mice. In addition, the chloroform
extraction achieved a 70 fold purification of C-076 from the whole broth.
Therapeutic Function
Antiparasitic
Safety Profile
A poison by ingestion.Moderately toxic by skin contact. When heated todecomposition it emits acrid smoke and irritating fumes.
Check Digit Verification of cas no
The CAS Registry Mumber 65195-55-3 includes 8 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 5 digits, 6,5,1,9 and 5 respectively; the second part has 2 digits, 5 and 5 respectively.
Calculate Digit Verification of CAS Registry Number 65195-55:
(7*6)+(6*5)+(5*1)+(4*9)+(3*5)+(2*5)+(1*5)=143
143 % 10 = 3
So 65195-55-3 is a valid CAS Registry Number.
InChI:InChI=1/C48H72O14/c1-11-25(2)43-28(5)17-18-47(62-43)23-34-20-33(61-47)16-15-27(4)42(26(3)13-12-14-32-24-55-45-40(49)29(6)19-35(46(51)58-34)48(32,45)52)59-39-22-37(54-10)44(31(8)57-39)60-38-21-36(53-9)41(50)30(7)56-38/h12-15,17-19,25-26,28,30-31,33-45,49-50,52H,11,16,20-24H2,1-10H3/b13-12+,27-15-,32-14-/t25-,26-,28-,30-,31-,33+,34-,35-,36-,37-,38-,39-,40+,41-,42-,43+,44-,45+,47+,48+/m0/s1
65195-55-3Relevant articles and documents
CHEMICAL DEGRADATION OF AVERMECTIN B1
Blizzard, Timothy A.,Mrozik, Helmut,Fisher, Michael H.
, p. 3163 - 3166 (1988)
Chemical degradation of avermectin B1 (1) affords two interesting and unexpected degradation products (3 and 7) in addition to several previously reported compounds.
A novel synthesis of avermectin B(1a) from avermectin B(2a)
Katoh, Tadashi,Itoh, Etsuko,Terashima, Shiro
, p. 587 - 590 (2007/10/03)
The title synthesis was achieved via a four-step sequence of reactions including selective silylation of the C4''- and the C5-hydroxy groups, mesylation of the remaining C23-hydroxy group, tetra-n-butylammonium oxalate- induced elimination, and deprotection of the silyl protecting groups.
Total synthesis of the antiparasitic agent avermectin B1a
White, James D.,Bolton, Gary L.,Dantanarayana, Anura P.,Fox, Christina M. J.,Hiner, Roger N.,Jackson, Randy W.,Sakuma, Kazuhiko,Warrier, Ulhas S.
, p. 1908 - 1939 (2007/10/02)
The synthesis of avermectin B1a has been completed by a route that assembles the aglycon from three subunits consisting of the hexahydrobenzofuran moiety (A), the spiroketal segment (B), and the acyclic portion (C) comprising C9-C15. Connection is made in a B + C → (B -C) + A sequence, and the synthesis is concluded by attachment to the aglycon of the L-oleandrosyl-L-oleandrose disaccharide via the pyridylthio glycoside.
