Crystallographic studies of an anthraquinone derivative obtained from kidamycin

TetrahedronLetters No. 13, pp 1065 - 1~68, 1973. Pergamon Press.

CRYSTALLOGRAPHIC

STUDIES

OF

OBTAINED

FROM

Minoru Research

Institute,

Daiichi

Faculty

of

Pharmaceutical

ANTHRAQUINONE

DERIVATIVE

KIDAMYCIN

Furukawa

Seiyaku

Akiko

AN

Printed in Great Britain.

Co.,

Itai,

Ltd.,

Yoichi

Sciences,

Edogawa-ku,

antitumor of

(I)

and

I ty

X-ray

Preliminary

University

of Tokyo,

the

presence

was

assumed

Hongo,

a compound

(III)

compound kept

in

large

crystals

of

III

Weissenberg

were and

orthorohmbic

c=10.18~. for

The the

to

in

flask

at

carry

out

from

sample

used

a mixed room

the

the

was

for

the

solution

solution

lattice

the

indicated constants

chemical

1065

II

reduction, Evidence

molecular

very

by

that

from fine

and to

elongated

by

methanol needles, as

ra-

analysis. ethyl

aceta-

obtain

a

prismatic

months. the

a=15.559,

P212121. formula,

I followed

X-ray

attempt

for

formula

methanolysis

methanol

several

several

dimethylamino

of

present

of

of

product

Large

after

to be

the

I as

in an

analysis.

determined

indicated

from

temperature

X-ray

the

of

studies.

to

Acetylation

(II)

chemical

oxygens. and

of

structure

presence

resistant

obtained

derived

been

the

the

methyls,

ethereal

form.

photographs

with

group

not

methoiodide

has

precession

space

dried

latter

and

crystallization

is presumably

grown

system

was

aromatic

possessing

determine

the

group(s)

duplicate

and

dissolved

a sealed enough

its

acetate

which The

(II)

an

and

group

linkage

iodide

gave

prisms.

crystal

sis

methyl

sec.

Japan

16 February 1973)

with

indicated

car-bony1

hydroxyl

or

to

simultaneously

tert.,

hydroxyls,

C 39H480gN2

acetate

as

Tokyo,

phaeoverticillatus

Attempts

experiments(2)

I such

a glycosidic

and

the

in

NMR

of

with

large

and

a chelated

ethyl

te was

proceeded

have

with

and

The

analysis

as

alkylation

Streptomyces

activities(l).

alcoholic

sec.

of

antibacterial

groups

carbonyl(s)

ther

a metabolite

chemical

functional groups,

is

Japan

Iitaka

(Received in Japan 29 January 1973; received in UK for publication Kidamycin

Tokyo,

The C

crystal

belongs

b=39.49, elemental

48H64013N212-

analyH2°-

to

No. 13

1064

Found

: C

: I 22.09.

N 2.44 using

a mixed

cm -3 which units

The

is

in

of

the

methanol

by

the

X-ray

data

l H 2 0*&H

four

circle

walled

of

times

The

of by

Fourier

use

of

mined

by

ttering

measured

are

and

contained of

the

ethyl

in

the

unit

and

the

using

crystal

immediately

was

cell.

three

was

deteriorated

The

presence

confirmed

computer

later

to

inten-

controlled

sealed

due

g

structure

dimensional

a Rigaku

:

method 1.36

four

was

specimen

: H 5.79

flotation

acetate

crystallization

constants

The

by

g cm -3 assuming

1.356

measurement

it

standard

of

a W-26

us

to

the

The the

diffractometer

were

in

a thin-

loss

of

the

final

using

of

was

intensities

with

above

Ni-filtered

of

Friedel

radiation

the

carried

The

CUKCZ

out

absolute

and

of

they

least-squares

by

the

atoms.

method were

of

were

compared

was for

taken

block-

allowed

corrections were

use calcu-

configuration

reflexions

were

four

parameters

CUKCL radiation pairs

Successive

seventy

Dispersion

method. for

all

method.

with

thermal

O-125.

atom

atom

coupled

anisotropic was

200

net

obtained

heavy

locations

iodine

CuKa

the

syntheses

dispersion

the

by

parameters

R value

having

method.

the

in which

Intensities

Aft'= 7.2.

deviations,

Fourier

structural

of

factors

solved

assign

anomalous

factors

structure

scan

was

difference

least-squares, atom.

the

since

structure

enabled

each

OH

value

a solvent

independent

their

and

Refinement matrix

1425

crystal

lations

3

diffractometer.

capillary

of

radiation

the

lattice

from

crystal

50.18

: C

crystallization.

A total three

The

derived

X-ray

glass

solvent

as

analysis.

the

Calculated

tetrachloride

with

molecules

were

of

carbon

agreement

of C48H64013N212

sity

density

solution

of

of

: H 5.86 : N 2.36 : I 21.99.

50.17

deter-

the

as Aft=

the

sca-1.1,

measured

with

for

on

the

calculated

value. The 1-a

molecular

excluding

crystal

as

structure cture

of

Ellipsoid

structure the

the

solvents

is given the

molecules

in

molecule.

Plot)

program

of Fig. The by

determined of

by

methanol

the and

present water A

crystallization. 1-b

which

figure Johnson(4)

shows was

the

drawn in which

by

analysis

which

are

stereoscopic three the the

is

contained drawing

dimensional ORTEP atoms

shown

(Oak were

in in

of

Fig. the

the

absolute Ridge drawn

stru-

Thermal by

the

No. 13

spheres The two minal

1067

of

varying

structure

radius consists

tetrahydropyrane methoxyl

Fig.

l-a

Fig.

l-b

and

with of

moieties acetoxyl

increasing

order

a tetracyclic attached groups

with

of

atomic

conjugated

to

the

the

ring

peri

ring D.

The

hydroxyl

numbers. A,B,C,D,

system presence group

in

of the

and the

ge-

ring

C

1068

of

the

present

structure

by methanolysis The

same

with

ring

indomycinone(3) The

system and

directly

except

for

should

be

also

the

conformation

the

are

The

atoms.

in

C-4"

the

trimethylamino

to

the

be

given

the

C-2'

both

the

group

methyl

each

while is

are

was

formed

both

bulky

would

to

come

Details

of

the

o

the

of

211S,311S F ring

may also

F ring

the

be

i ca

at C

attached

diaxial and

configur

are

groups

If

study

conformations

rings II C-2 , and

cis-1,3

this

F r

that

trimethylamino direction.

in

two

and

at C-2'

equatorial

group.

the

a similar the

F ring

while

fo

aromatic

absolute

the

of

been

should

the

at C-4'

The

form

has

have

and

of

conformations

the

rings

other.

a chair

to

group

those

III

indomycins(3)

linked

methyl

configurations

in

III

of

configurations

from

the

rings,

oriented

and

(III)

that

I and

The

a tertiary

E ring

in

F in

bonds.

differ

the

In both

are

of

that

difference

differences

C-4M

C-C

2'R,3'S,4'R,6'R, of

compound

as

between

E and

the

rings

E ring

the

chromophore

similarity

presence

noted

the

took

(

a

position

w

constitution

elsewhere.

: The authors

Acknowledgement Dr.

the

the

rings

tetrahydropyrane

form.

of

through

the

that

rearrangement.

tetrahydropyrane

atoms

indicates

Takeo

Ishiguro

thank

of Daiichi

Toju

Prof.

Seiyaku

Co.,

Hata

Ltd.

of

for

Kitasato

their

kind

Unive: arrangt

interest.

References la)

T.Hata,

I.Umezawa,

Progress Press), b)

K.Komiya,

and

in Antimicrobial. 1, 88

N.Kanda,

J.

K.Asano,

Anticancer

B.Fujita

Chemotherapy

and

M.Kon

(Universit:

(1971).

Antibiotics I-Hayakawa

(Tokyo) and

M.Furukawa,

3)

H.Brockmann,

Angew.

Chem.

4)

C.K.Johnson,

ORTEP,

ORNL-3794,

U.S.A.

24,

G.Ohta,

2)

Tennessee,

N.Kanda,

Internat. Oak

599

(1972).

unpublished. Edit. Ridge

7,

481

National

(1968). Laboratory,

Oak