Total synthesis of phenolic Balfourodendron alkaloids

Tetrahedron Letters,Vo1.24,No.23,pp Printed in Great Britain

2359-2360,1983

0040-4039/83 $3.00 + .OO 01983 Pergamon Press Ltd.

TOTALSYNTHRSISOF PHENOLIC BALFOURODENDRON AXAIX)IDSl Corral,

A.

Rexhe

Orfeo 0. Orasi’

and Juan C. Autino

Facultad de Clencias Rxactas, Universidad Naclonal de La Plata, 47 y 115, (1900) La Plata, Argentina is reported; Summary. The total synthesis of (f)-rlballne earlier findings, this represents a formal total synthesis Numerous dihydrofuro ted from Rutaceae2 routes

or dihydropyrano

(e.g.

2-quinolone

of diethyl

prenyl

bromide(l.1

been dissolved

product

solvent,

of the extract

(NMR: 56

yield

45% yield)

The cyclleatlon

details

for

this

at 12 h Intervals

the residue

of V via its

epoxlde

examples. 5

To remove

were again added, the After

eva-

of the crude

IV) which gave pure V (m.p.

from C6H6 and then from EtOAc.’ to give

the phenolic

2359

12 h,

with 1 N NaOHaq;

with AcOH caused the precipitation

crystallization

(48 h):

After

that of the preceding.

of V and 24% of unreacted

after

step are

of these reagents;

was extracted

of IV at

mmol) which had

mm011 in toluene

crude VI(extracted

1 M H3P04aq; showed mainly one spot on TLC; 95% yield) analogous

prenylatlon

ml) was added to IV(l

each time to one half

of the organic

140-141Q;

additions

cy-

(see Scheme).

out at 359 under N2 with stirring

ml> and prenyl bromide(0.55

amounts were decreased

acidification

was carried

mmol) in toluene(1

by two further

poration

and operational

for this

in 1 N NaOHaq(1 ml) and mixed with C6H6(l,25 ml).

2 N NaOHaq(0.25 followed

to give the 4-hydroxy-

of the route was the regioselective

The reaction

critical.

function.

employed tricarbethoxymethane and decarboxylation

C3 which led to V; the conditions

and several

a phenolic

malonate3 and II failed

by hydrolysis

Another key feature

species)

of examples bearing

IV, we have successfully followed

clleatlon,

synthesis

have been isola-

of some of the compounds. 3

with regard to synthesis

here the first

Since the reaction

alkaloids

Lunasia and Balfourodendron

have been reported

We report

qulnolinlc

in combination with of (t)-rlbalinidine.

protective

at OQ with

was done similarly group,

to

the crude VI

2360

(0.1 mmol) was heated at 1OOQ for 30 min In AcOH(O.3ml) and 0.2 M H,SO~aq(0.3 ml).

Addition of NaOAc(O.15 mmol) and plcrlc acld(O.1 mm011 in AcOH(O.2 ml)

gave a 77.$yield of (?)-ribaline(VI1)as picrats salt, m.p. 221-2230 dec.(from alcohol). The latter was identical to an authentic sample6 via comparison of mixed m.p. and IR spectra. This also represents a total synthesis of (+I-riba. linidlne(VIII), a phenolic dlhydropyrano-4-quinolonealkaloid, for earlier6 we had

described the isomerizatlon of (Z)-ribaline(VI1) to (+)-VIII.

HO

RO

R-C1/Me2C0 N/At dH3

+

N/AC

K2C03

RO

KOH/CH30H-H20

+ I

N2; 70Q;16 h II

h,

N/H CH3

(93%; picrate m.p. 86-879)

(901;m.p. 44-45Q)

OH

1) 2.5N KOHaq; CH(C02Et)3; N2 Dowtherm-A Reflux; 0.5 h

2) 25~;

III

CH 3 (75Yi;m.p. 118-119Q)

-+O;cJ++, (see

text)

AcOH (74%;m.p. 221-222Q)

Ho&p;II

(=pG-CH30_CH2-I

3

3

References 1) Part XXIII of "Studies on Plants"; J.C.A. is doing his doctoral thesis on this subject. Preceding part, R.A. Corral, 0.0. Orazl and M.E. Gonzilez, Rev. Latlnoamericana Quim., 2, 184 (1978). 2) I. Mester, Fitoterapia, 4C, 123 (1973); 41, 268 (1977). 3) L.A. Hltscher, T. Suzuki, G. Clark and M.S. Bathala, Heterocycles, 2, 565 (1976). 4) All new compounds I-V gave satisfactory spectral and analytical data. 5) J.L. Gaston and M.F. Grundon, J.C.S. Perkin I, 2294 (1980). 6)

R.A. Corral, 0.0. Orazi and I.A. Benages, Tetrahedron, 3, (Receivedin USA 11 January

1983)

205 (1973).