Synthesis of β-carbolinyl sugars

Carbohydrate Resrmch Elsevier Publishing Company, Amsisrdam Printed in Belgium

414

SYNTHESIS Yu.

A.

OF /3-CARBOLINYL

ZHDANOV,

The Rostou-on-Don

SUGARS

V. I. KORNILOV,AND G. N.

DOROFEENKO

State Unicersity, Rostoo-on-Don

(U. S. S. R.)

(Received June 14th. 1967; in revised form, December 20th, 1967)

,

ABSTRACT

Decomposition of penta-O-acetyl-l-deoxy-l-diazo-keto-D-gluca-heptulose, in the presence of N-methylindole and copper powder as catalyst, results in the formation of penta-O-acetyl-l-deoxy-l-(N-methylindol-3-yl)-keto-D-gZ~co-heptulose (1). Compound 1 is acylated by carboxylic anhydrides at C-2 of the iV-methylindole moiety, and cyclisation of the intermediate diketone, in the presence of 70% perchloric acid, gives indolo-[2,3-cl-pyrylium

perchlorates.

With aqueous ammonia, these perchlorates carbolinyl sugars that are close structural analogues harmine, and melinonine.

are easily transformed into /3of the indole alkaloids harmane,

INTRODUCTION Although there exists a great variety of methods’ for the synthesis of sugars having heterocyclic C-substituents, similar compounds containing the alkaloid-like system of fl-carboline were hitherto unknown. Lobry de Bruyn and Alberda van Ekenstein2 tryptamine

failed to synthesise j?-carbolinyl according to the Pictet-Spengler

derivatives by condensing method3*4.

D-glucose

with

We thought it worthwhile to synthesize fi-carbolinyl sugars, which are near structural analogues of the indole alkaloids, harmane, harmine, melinonine, and others’. EXPERIMENTAL Infrared spectra (mineral oil) were obtained with a HKC-14 spectrophotometer. Ultraviolet spectra were recorded for methanolic solutions (IO-%) with a Q-4 spectrophotometer. Polarimetry of the products was precluded by their intense colours. Perzta-O-acetyl-I-deoxy-l-(N-merlzyZindol-3-yl)-keto-D-glucq-heptulose (1). To a mixture of N-methylindole (3 g, 0.02 mole), dry toluene (5 ml), and a catalytic quantity of copper powder at 95-IOO”, was added dropwise a solution of penta-& acetyl-1-deoxy-I-diazo-kero-D-glrrco-heptulose6 (4.3 g, 0.01 mole) in toluene (50 ml), Curbohyd. Res., 6 (1968) 414417

~CARBOLINYLSUGARS

415

Liberation of nitrogen began at once, and when this was complete, the catalyst was filtered off, and toluene was removed in caczto. The residual syrup was treated 5 or 6 times with light petroleum and then dissolved in benzene (50 ml), and the solution was gradually poured into light petroleum (500 ml). The product separated as a dark syrup that was dissolved in chloroform-methanol (19:1), and the solution was shaken with a small quantity of alumina for several hours. The alumina was filtered off, and the filtrate was evaporated in oacuo. The residue was dissolved in benzene (50 ml), and the solution was poured into light petroleum (500 ml). The crude product was precipitated as an amorphous, yelIow powder, and was purified by repeated reprecipation from light petroleum: the material precipitated initially was discarded_ The title compound (1.8 g, 29%) was finally obtained as an amorphous, yellow powder that was soluble in most organic solvents, but insoluble in water and light petroleum, and had vFatl 1756 (OAc), 1723 (C = 0), 1640, I510 (heterocycle), and 1222 cm- ’ (C-O-C); vg; 2812cm-’ (>N-CH,); E,,, 222 (E 26,500) and 282 nm (6,200) (Found: C, 58.20; H, 5.88; N, 2.80. C,,HXINO,, talc.: C, 58.53; H, 5.81; N, 2.62%). I,9-Dimetfzyf-3-~~-gIuco-pentaacetoxy~e~ztyl)-~-car6o/ine (4a). Perchloric acid (70%, 0.8 ml) was added dropwise to compound 1 (4 g, 0.007 mole) dissolved in IO ml of acetic anhydride. After 15-20 min, the highly resinous mixture was diluted with 200 ml of ether. The resulting, dark-brown residue of the perchlorate 3 was carefully ground with ether, filtered off, and washed several times with ether in order to remove anhydride. The product was suspended in ether and treated with an excess of 20% aqueous ammonia. The product was extracted 5-10 times with ether, and the dried (Na,SOJ extract was purified with charcoal. The solvent was distilled off, leaving compound 4a (1g, 25%) as an amorphous, yellow powder. Further purification of the product was effected by repeated reprecipitation from chloroform (with light petroleum); the first material to be precipitated was discarded in each case. The product was soluble in most organic solvents, but not in water and light petroleum, and had v,,, N3C11736 (OAc), 1624, 1603, 1535, 1485 (heterocycle), and 1218 cm- 1 (C-O-C); R,,, 239 (E 24,200), 278 nm (i4,OOO) (Found: C, 60. I I ; H, 5.96; N, 4.78. C,8H3tN20,0 talc.: C, 60.43; H, 5.75; N, 5.03%). I-EthyI-9-?nethyf-3-(D-gluco-pentaacetoxypentyl)-P-carboline (4b).- According to the directions given for obtaining compound 4a, compound 1 (2 g, 0.003 mole) was treated with propionic anhydride (5 ml) and perchloric acid (0.4 ml) to &give compound 4b as an amorphous, yellow powder (0.61 g, 29%); vF$’ 1748 (OAc), 1630, 1604, 1538, 1489 (heterocycle), and 1215 cm-’ (C-O-C); &,,,238 (E 24,200), 279 nm (14,000) (Found: C, 61.31; H, 5.97; N, 5.21. Cz9H34N2010 talc.: C, 61.05; H, 5.96; N, 4.91%). 9-~~etfyf-3-(D-gIuco-pentaacetoxypentyf)-l-propyf-~-carbofine (4~). According to the procedure described for the preparation of compound 4a, compound 1 (2 g, 0.004 mole) was treated with butyric anhydride (5 ml) and perchloric acid (70%, 0.4 ml) to give compound 4c (31%) as an amorphous, yellow powder that was soluble in most organic solvents, insoluble in water and light petroleum, and had ~2~:’ 1745 (OAc), 1624, 1610, 1530, 1499 (heterocycle), and 1217 cm-’ (C-O-C); Curbohyd. Res., 6 (1968)414417

W.

416

A. ZHDANOV,

V. I. KORNILOV,

G. N. DOROEEENKO

Am,,238 (a 24,2OO),278 nm (14,000) (Found: C, 62.70; II, 5.30; N, 4.81. C3tHs6N201 a talc.: C, 62.41; Ii, 5.36; N, 4.69%). DISCUSSION

The oxocarbenes formed by the decomposition of diazoketoses, in the presence of copper powder, attack7*8 C-3 of N-mcthylindole (Scheme 1). to give l-deoxy-l(N-methylindol-3-yl)-ketose acetates. Penta- O-acetyl- I-deoxy-(N-methylindo2-3-yl)-

CHNz

E-4

I c=o

I c==o

I AcOCH I

HCOAc I HCOAC

I CH,ObK

&

I HCOAc

I HCOAC &

I AcOCH

\

o%, I

I

C===O I HCOAc

I

I

HCOAc I

ACOCH

I HCOAc

HCOAc

I CH,OAC

I H CQAC I C+OAc Scheme

1

Cicero-D-gluco-heptulose(1)is an amorphous, coloured powder. Its study by polarimetry is impossible because of the intense colour of its solutions. The intense bands at 1756 and 1222cm-’ in the i.r. spectrum are characteristic of the ‘acetyl groups, and the weak bands at 28 12, 1640, and 15 10 CM- ’ may be assigned to the N-methylindole moietyg. The U.V. spectrum, having I,,,, 222 (E 26,500) and 282 nm (6,200), was similar to those of indole derivativcss. Indolylacetone and alkylindolylacetones are acylated” at C-2 by carboxylic anhydrides in the presence of 70% perchloric acid to yield indolo-f2,3-cl-pyrylium perchlorates. In order to obtain C-substituted indolopyrylium salts and carbolines, we investigated the acylation of compound 1 with acetic, propionic, and butyric anhydrides in the presence of 70% perchloric acid. The acylating agents in these reactions are acyl perchlorates”. The diketone 2, formed as an intermediate in the presence of perchloric acid, cyclises to give the pyrylium salt 3. The reaction is accompanied by resin formation and a consequent lowering of the yield of the final product. The acylation of indol-3-ylketoses having an unsubstituted nitrogen atom have not been studied, since, in this case, acylation of indole, and a number of other processes connected with the Iabihty of the indole system in strongly acid media are possible. In the acylations of indol-3-ylacetone, the yield of products does not exceed 20%. The ease with which a pyrylium oxygen atom is replaced by nitrogen makes itpOssib~P;t~o~~crt~ndd~[2,3-~3~~ry~iuM sahsinto derivatives ofp-carbohne. The transformation of pyryhum salts 3 into &carbolines 4 took place directly at room temperature- The i.r. spectra of the &carboZinyl sugars (4) showstrong bands at Carbo&v.?. Rex., 6 (EJ68) 4144f

7

@ARBOLINYL

417

SUGARS

1750-1736 and 1220-1214 cm-‘, which are regions that are characteristic of the acetylated sugar moiety. The bands at 1630, 1600,1530, and 1500 cm-’ are consistent A

(R’C0120 HaO

CH 2 -E-R

o”c

4

‘ir’

c=o 51 C&R

2

40

R’=Me

4b

R’=Et

4c

R’=Pr

H&Ok R=

3

AcO&H

t

HCOAc I HtoAc CH20Ac Scheme

2

with the heterocyclic moiety. There was no band characteristic of a free carbonyl group’, and the band in the region 1750-1730 cm-’ was narrow. REFERENCES 1 Yu. A. ZHDAN~V AND G. N. DOROFEENKO, Kbimicheskie precrashchettija ug~erodrtogo skelelo aglecodou, Akad. Nauk SSSR, Moscow, 1962. 2 C. LOBRY DE BRUYN AND W. ALBERDAVAN EKFINSTEIN, Bet-., 31(1898)2476. 3 W. M. WHALEY AND T. GOVINDACHARI, Org. Reactions,6 (1951)74. 4 1%‘.0. KERMAC~AND 3-E. MCKAIL, in R. C. ELDERFIELD (Ed.), Heterocyclic Compotmds, Vol. 7, Wiley, New York, 1961, p. 185. 5 H. G. BOIT,Ergebnisse der alcaloid Chemie bis 1960, Berlin, 1961. 6 M.L. ~Vo~~aaht,S.\N.W~lsaao-t,~~~R L, Bmwm,.T. Am.Chem. &x.,64 (1942) 1701. 7 Yu. A. ZHDANOV,~. I. KORNILOV, AND G.V. BOGDANOVA, Carbohyd. Res.. 3 (1966) 139. 8 Yu. A. ZHDANOV, V. 1.KORNILOV, AND G. V. BOGDANOVA, Carboh_vd. Res.,4 (1967) 492. 9 K. NAKANISHI, Infrared Absorption Spectroscopy, Nankodo, Tokyo, 1962. 10 G. N. DOROFEENKO AND L. V. DULENRO, Khim. Gererotsiki. Soedin., Akad. Nauk Lato.SSR, in press. 11 G. N. DOROFEENKO, Yu. A. ZHDANOV, V. I.DULENKO, AND S.-V.KRIXUN, Kchlornaja kisfotu i ee soedinenQa u organicheskom sinteze, Rostov-on-Don, 1965. Carbohyd. Res., 6 (1968) 414417