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Olivomycin. II. Structure of the carbohydrate components
Tetrahedron Letters No.*'l, pp. 3513-3516, 1964. Printed in Great Britain.
Pergamon PressLtd.
OLIVOMYCIN. II. STRUCTURB OF TBE CARBOHYDMTRcOMPONENTs Yu.A.Berlin, S.E.Eeipov, M.N.Kolosov and Y.Y.Shemyak3.n Institute for Chemistry of Natural.Products USSR Academy of Sciences, Moscow, USSR and &G.Brazhnikova Institute for New Antibiotics Research USSR Academy of Medical Sciences, Moscow, USSR (Received 5 October 196r)
EARLIER we reported the isolation of several sugar derivatives from the acid methanolysis products of the antibiotic olivowcin
(1). The present communication shows that the corres-
ponding sugars u&ich we have called olivomycose, olivomoee and olivose possess the structures (I), (III) and (IV), respectively. Olivo4ycose C$,404
has three hydroql
groups, two C-
methyl groups, in the form of CH3- -0 (doublet at 1.30 ppm H with J = 6 cps) and CH3 -0 (singlet at 1.25 ppm), as well f as aCH2 -0 fragment (a group of peeks in the region of -! 1.80 ppm and a quadruplet at 4.35 ppm). (The 6 values pertain to the p-methyl olivorqycoside)(2). The sugar reduces 2 moles of periodic acid yielding 1 mole of HCOOH, whereas its glycosides consume 1 mole of HJ04 without formation of volatile products. It follows from these data that olivongrco-
3513
3514
No.47
se ham the structure of a 3-C-metbyL2,6Xiideoxyhexose. The
configuration of it8 C3, C4 and C5 asymmetric centers were elucidated as follows. Tosylation of methyl olivomycoside (TsCl + Py, 20') gave a monotosylate, which on treatment with 0.4 H methanolic NaOH was readily converted into the 3,4oxide
(IL~.IO~~,
subl.). Moreover it was found that the
LMI436 of ~-methyl olivomycoside in cuprammooium solution (0.2 mole Cu and 13 moles NH
per liter) undergoes a consider3 able negative shift (ACu -1670') which indicates a value of -6OO for the projected valency angle between the C3-0 and c4-0 bonds (cf.(J)). From this there follows the trans-diequatorial arraugement of the hydroxyls at C3 and C4 in the IC conformation of the pyranose ring, which is stable only providing the methyl group at C5 is in equatorial position. Hence OlivO~COse is 3-C-methyl-2,6-dideoxy-L-arabo-hexose(I).
It had previously been shown that in the antibiotic itself olivomcose is in the form of the isobutyratc (1). We found that the latter resists periodate oxydation and therefore its acyl residue must be at C4-CH (II). Finally, since olivomycose belongs to the L-series, the previously described (1) levorotatory methyl isobutyrylolivomycoside A and methyl olivomycoside A are d-glycosides. For the second degradation product, olivomose C7H,40,+, the structure 2,6-dideoxy-4-O-methyl-D-hexosewas established
3515
No.47
(1).
AlQlation
Ag20
gave
of its d-methyl glycoside by means of c+,J
the methyl ether ([d]g3
+
+133'; c 0.6, BtOH), which
proved to be identical with the d-methyl 3,4-di-O-methyl2,6-dideoxy-D-galactopyranosidewe synthesized from d-methyl 2-deoq-D-galactopyrsnoside by selective 6-tosylation followed by methylation and then LiAlB4 reduction. In this way it was shown that olivomose is k-0-methyl-2,6-dideoxy-D-mhexose (III). OMe
The third cerbobydrate component of olivomyci~, olivose c6H12049 is 2,6-dideom-D-hexose (1). Besides its d-glycoside, we were able to isolate b-methyl olivoside, [d] g2 -a5O (c 1, EtOH), m.p.84' (from B~OAC-C~H,~). The change in [M]436 of this substance in cupremmonium solution (ACU +2120°, i.e. a projected valency angle of +60°) indicates a diequatorial arrangement of the hydroxyls at C3 and C4 (conformation Cl). Olivose is therefore 2,6-dideoxy-D-arabo-hexose (Iv). It is noteworthy that similar sugars have been found among the constituents of other antibiotics. Thus, the 4-0isovalelrglderivative of mycarose (the C3 epimer of olivomycose) is contained in the magnamycins (4,5), and chromose B, the acetyl derivative of olivomycose, has been revealed in chromomycin A
3
(6). Two other deo&y sugars have been iso-
3516
No.*7
lated from chrowoqycinA3
which
appear to be closelyrelated
to olimmose and olivose (6,7).Regrettablythe insufficient characterization of these deoxy sugars and a certain divergence between&heir constantsand those of our compoundedo not allow of conclusivedecisionconcerningthe identityof these substences.
1. Yu.A.Be.rlin, S.E.Esipov,M.N.Kolosov,M.Y.Sheqakin, M.G. Brashnikwa, TetrahedronLetters,12#, -w 1323; reportedto the InternationalCongress on Autibiotics(Prague,June 1964).
2. NHR spectraldata, for which the authors are grately iudebted to Dr. G.Yu.Peck,were obtainedon a 60 Rc instrument in CDC13 solution,with Me4Si as internalstaudard. 3. B.E.Beeves,
Advances &
CarbohvdrateChewistq, 9, 108
(1951).
4. P.P.Begna,F.A.Hochsteiu,R.L.Waguer,R.B.Woodward,J.&. m.&.
, 22, 4625 (1953).
5. D.Y.Lemal,P.D.Pacht,R.B.Woodward,Tetrahedron,18, -= 1275
(1962). 6. M.Miyawoto,Y.Kawsmatsu,M.Shinohara,K.Neksuishi,Y.Nakadaira, N.S.3hacca, -TetrahctlronLetters, 'll64, __== 2371. 7. hi*;. Miyam,to, Y .Kawamatsu, hi. Shinohara, Y .Asahi, Y.Nakadaira, H,Kalclsawa,K.Nakanishi, N.S.Bhacca, Tetrahedron Letters, $!ZGJ,693.
Pergamon PressLtd.
OLIVOMYCIN. II. STRUCTURB OF TBE CARBOHYDMTRcOMPONENTs Yu.A.Berlin, S.E.Eeipov, M.N.Kolosov and Y.Y.Shemyak3.n Institute for Chemistry of Natural.Products USSR Academy of Sciences, Moscow, USSR and &G.Brazhnikova Institute for New Antibiotics Research USSR Academy of Medical Sciences, Moscow, USSR (Received 5 October 196r)
EARLIER we reported the isolation of several sugar derivatives from the acid methanolysis products of the antibiotic olivowcin
(1). The present communication shows that the corres-
ponding sugars u&ich we have called olivomycose, olivomoee and olivose possess the structures (I), (III) and (IV), respectively. Olivo4ycose C$,404
has three hydroql
groups, two C-
methyl groups, in the form of CH3- -0 (doublet at 1.30 ppm H with J = 6 cps) and CH3 -0 (singlet at 1.25 ppm), as well f as aCH2 -0 fragment (a group of peeks in the region of -! 1.80 ppm and a quadruplet at 4.35 ppm). (The 6 values pertain to the p-methyl olivorqycoside)(2). The sugar reduces 2 moles of periodic acid yielding 1 mole of HCOOH, whereas its glycosides consume 1 mole of HJ04 without formation of volatile products. It follows from these data that olivongrco-
3513
3514
No.47
se ham the structure of a 3-C-metbyL2,6Xiideoxyhexose. The
configuration of it8 C3, C4 and C5 asymmetric centers were elucidated as follows. Tosylation of methyl olivomycoside (TsCl + Py, 20') gave a monotosylate, which on treatment with 0.4 H methanolic NaOH was readily converted into the 3,4oxide
(IL~.IO~~,
subl.). Moreover it was found that the
LMI436 of ~-methyl olivomycoside in cuprammooium solution (0.2 mole Cu and 13 moles NH
per liter) undergoes a consider3 able negative shift (ACu -1670') which indicates a value of -6OO for the projected valency angle between the C3-0 and c4-0 bonds (cf.(J)). From this there follows the trans-diequatorial arraugement of the hydroxyls at C3 and C4 in the IC conformation of the pyranose ring, which is stable only providing the methyl group at C5 is in equatorial position. Hence OlivO~COse is 3-C-methyl-2,6-dideoxy-L-arabo-hexose(I).
It had previously been shown that in the antibiotic itself olivomcose is in the form of the isobutyratc (1). We found that the latter resists periodate oxydation and therefore its acyl residue must be at C4-CH (II). Finally, since olivomycose belongs to the L-series, the previously described (1) levorotatory methyl isobutyrylolivomycoside A and methyl olivomycoside A are d-glycosides. For the second degradation product, olivomose C7H,40,+, the structure 2,6-dideoxy-4-O-methyl-D-hexosewas established
3515
No.47
(1).
AlQlation
Ag20
gave
of its d-methyl glycoside by means of c+,J
the methyl ether ([d]g3
+
+133'; c 0.6, BtOH), which
proved to be identical with the d-methyl 3,4-di-O-methyl2,6-dideoxy-D-galactopyranosidewe synthesized from d-methyl 2-deoq-D-galactopyrsnoside by selective 6-tosylation followed by methylation and then LiAlB4 reduction. In this way it was shown that olivomose is k-0-methyl-2,6-dideoxy-D-mhexose (III). OMe
The third cerbobydrate component of olivomyci~, olivose c6H12049 is 2,6-dideom-D-hexose (1). Besides its d-glycoside, we were able to isolate b-methyl olivoside, [d] g2 -a5O (c 1, EtOH), m.p.84' (from B~OAC-C~H,~). The change in [M]436 of this substance in cupremmonium solution (ACU +2120°, i.e. a projected valency angle of +60°) indicates a diequatorial arrangement of the hydroxyls at C3 and C4 (conformation Cl). Olivose is therefore 2,6-dideoxy-D-arabo-hexose (Iv). It is noteworthy that similar sugars have been found among the constituents of other antibiotics. Thus, the 4-0isovalelrglderivative of mycarose (the C3 epimer of olivomycose) is contained in the magnamycins (4,5), and chromose B, the acetyl derivative of olivomycose, has been revealed in chromomycin A
3
(6). Two other deo&y sugars have been iso-
3516
No.*7
lated from chrowoqycinA3
which
appear to be closelyrelated
to olimmose and olivose (6,7).Regrettablythe insufficient characterization of these deoxy sugars and a certain divergence between&heir constantsand those of our compoundedo not allow of conclusivedecisionconcerningthe identityof these substences.
1. Yu.A.Be.rlin, S.E.Esipov,M.N.Kolosov,M.Y.Sheqakin, M.G. Brashnikwa, TetrahedronLetters,12#, -w 1323; reportedto the InternationalCongress on Autibiotics(Prague,June 1964).
2. NHR spectraldata, for which the authors are grately iudebted to Dr. G.Yu.Peck,were obtainedon a 60 Rc instrument in CDC13 solution,with Me4Si as internalstaudard. 3. B.E.Beeves,
Advances &
CarbohvdrateChewistq, 9, 108
(1951).
4. P.P.Begna,F.A.Hochsteiu,R.L.Waguer,R.B.Woodward,J.&. m.&.
, 22, 4625 (1953).
5. D.Y.Lemal,P.D.Pacht,R.B.Woodward,Tetrahedron,18, -= 1275
(1962). 6. M.Miyawoto,Y.Kawsmatsu,M.Shinohara,K.Neksuishi,Y.Nakadaira, N.S.3hacca, -TetrahctlronLetters, 'll64, __== 2371. 7. hi*;. Miyam,to, Y .Kawamatsu, hi. Shinohara, Y .Asahi, Y.Nakadaira, H,Kalclsawa,K.Nakanishi, N.S.Bhacca, Tetrahedron Letters, $!ZGJ,693.