Browse Prior Art Database

Process for the preparation of (2R,6S,9S,11R,12S,14aS,15S,20S,23S,25aS)-12-(2-Aminoethylamino)-20-[3-amino-1(R)-hydroxypropyl]-23-[1(S),2(S)-dihydroxy-2-(4-hydroxyphenyl)ethyl]-9-(10,12-dimethyltetradecanamido)-2,11,15-trihydroxy-6-[1(R)-hydroxyethyl]perhydrodipyrrolo[2,1-c:2',1'-l][1,4,7,10,13,16]hexaazacycloheneicosine-5,8,14,19,22,25-hexaone diacetate, via new intermediate.

IP.com Disclosure Number: IPCOM000196342D
Publication Date: 2010-May-31

Publishing Venue

The IP.com Prior Art Database

This text was extracted from a PDF file.
This is the abbreviated version, containing approximately 27% of the total text.

Page 1 of 10

Process for the preparation of (2R,6S,9S,11R,12S,14aS,15S,20S,23S,25aS)-12-(2- Aminoethylamino)-20-[3-amino-1(R)-hydroxypropyl]-23-[1(S),2(S)-dihydroxy-2- (4-hydroxyphenyl)ethyl]-9-(10,12-dimethyltetradecanamido)-2,11,15-trihydroxy- 6-[1(R)-hydroxyethyl]perhydrodipyrrolo[2,1-c:2',1'-
l][1,4,7,10,13,16]hexaazacycloheneicosine-5,8,14,19,22,25-hexaone diacetate, via new intermediate.

(2R,6S,9S,11R,12S,14aS,15S,20S,23S,25aS)-12-(2-Aminoethylamino)-20-[3-amino- 1(R)-hydroxypropyl]-23-[1(S),2(S)-dihydroxy-2-(4-hydroxyphenyl)ethyl]-9-(10,12- dimethyltetradecanamido)-2,11,15-trihydroxy-6-[1(R)- hydroxyethyl]perhydrodipyrrolo[2,1-c:2',1'-
l][1,4,7,10,13,16]hexaazacycloheneicosine-5,8,14,19,22,25-hexaone diacetate ("CASP") of the following formula:

NH

N

NH2

HN

O

OH

O

HO

NH

H2N

O

O

O

HN

OH

HO

O

O

NH H

N N

HO

OH

x 2 AcOH

OH

HO

CASP

is a semi-synthetic lipopeptide compound of the echinocandin family and represent a new class of antifungal agents.

    Hereinafter, is described a new process for the preparation of CASP via a new intermediate of the following formula:

NH

N

R

S

O

OH

O

HO

NH

O

H2N

O

HO

O

O

HN

OH

O

O

NH H

N N

HO

OH

OH

H

O

II

Page 2 of 10

R

HO

O

OH

S

O

OH

O

O

HO

NH

N

HO

NH

NH

N

NH

O

O

H2N

O

HO

O

O

HN

OH

H2N

O

HO

O

O

HN

OH

R-CH2-SH, acid /ACN

1.) PhB(OH)2, Mol. Sieve/THF
2.) BH3xSMe2
3.) HCl
4.) Chromatography

O

O

NH H

N N

O

O

NH H

N N

HO

HO

OH

OH

OH

OH

HO

I II

III IV

HO

R

R O

S

O

OH

S

O

OH

O

HO

O

NH

N

HO

NH

NH

N

NH

H2N

O

H2N

O

O

O

HN

OH

O

O

HN

OH

NH

H

N N

HO

HO

O

O

OXONE,
acetic acid /water

O

O

NH H

N N

HO

HO

OH

OH

OH

OH

HO

1.) H2NCH2CH2NH2

2.) Chromatography

CASP

HO

NH2

HN

O

OH

O

HO

NH

N

NH

H2N

O

O

O

HN

OH

HO

O

O

NH H

N N

HO

OH

x 2 AcOH

OH

H

O

EXAMPLES:

NMR spectra were taken on a Bruker DRX 500 instrument at 500.13 MHz for 1H and at 125.78 MHz for 13C measurement in DMSO-d6 solution. The chemical shifts were referenced to the solvent signal and expressed in δ (ppm) scale.

Assignment of the proton and carbon NMR data were done using two dimensional methods and comparison with the literature data.

Page 3 of 10

Mass spectra were obtained on a Bruker micrOTOFQ spectrometer using electrospray ionization.

-

1

[(

-

12

-

)

aS

25

S,

23

S,

20

S,

15

aS,

14

R,

12

R,

11

S,

9

S,

6

R,

2

(

of

Preparation

:

1

Example
-

4

(

-

2

-

dihydroxy

-

)

S

(

2

,

)

S

(

1

[

-

23

-

]

hydroxyethyl

-

)

R

(

1

-

Carbamoyl

-

2

[

-

20

-

]

thio

)

butyl

hydroxyphenyl

)

ethyl

-

]

(

-

9

-

,12

10

)

dimethyltetradecanamido

-

-

,15

,11

2

-

xy

trihydro

-

6

(

1

[

)

R

-

hydroxyethyl

perhydrodipyrrolo

]

-

,1

2

[

c

:

',

2

1

-

'

-

hexaazacycloheneicosine

]

,16

,13

,10

,7

,4

1

][

l (2R,6S,9S,11R,12R,14aS,15S,20S,23S,25aS)-20-[2-Carbamoyl-1(R)-hydroxyethyl]- 23-[1(S),2(S)-dihydroxy-2-(4-hydroxyphenyl)ethyl]-9-(10,12- dimethyltetradecanamido)-2,11,12,15-tetrahydroxy-6-[1(R)- hydroxyethyl]perhydrodipyrrolo[2,1-c:2',1'-
l][1,4,7,10,13,16]hexaazacycloheneicosine-5,8,14,19,22,25-hexaone (676.7 g; assay: 92,1 %; 623.2 g; 0.585 mol) was suspended in acetonitrile (18 liter)in an at least 50 liter jac...

Processing...
Loading...