July 5 , 1055
COMMUNICATIONS TO THE EDITOR
3677
21.12. Found: N, 21.191. Treatment of VI with dilute sodium hydroxide gave a product (VII) which formed a 2,4-dinitrophenylhydrazone1m.p. 205-206" dec. [Calcd. for C16H16N404: C, 56.96; H, 5.08; N, 17.71, mol. wt., 316. Found: C, 56.78; H I 5.16; Tu', 17.48, mol. wt., 3211. The ultraviolet spectrum had a maximum a t 402 mM, E 75,800 conP A U LF. ~ V I L E Y sistent with an a#- y,d-unsaturated carbonyl 2,4KOERTGERZON dinitrophenylhydrazone. E D W I NTI. FLYNN The first seven carbon atoms of I must be reprcM A XV. SEAL, J R . sented by the two seven-carbon compounds isoLT C A R O LQUARCK lated since these are the only ones containing the
The quantitative periodate oxidation experiments on TI1 and IV indicate the presence of a single 1,2-glycol grouping in I11 and the appearance of a second one in I V a s a result of the removal of desosamine. This evidence shows that desosamine is linked to one or the other of the carbon atoms involved in this second group. TALLY
RESEARCH
LABORATORIES
INDIANAPOLIS 6, INDIANA
RECEIVED J U N E 4, 1955
//O
grouping of I. The presence of a second carboxyl in I1 and the hydroxylactone nature of I11 are consistent with periodate oxidation of I to an aldehyde-acid followed by oxidation to I1 or reduction to 111. This also establishes the structure of 111. In conjunction with the previous evidence1 regarding the ester or lactone grouping in I, the following partial structure can be written for I. -c-0-
ERYTHROMYCIN. V. ISOLATION AND STRUCTURE OF DEGRADATION PRODUCTS
Sir: Periodate oxidation of dihydroerythronolide (I) followed by alkaline hydrolysis and oxidation gave an acid (11). This acid was identified as a,a'dimethyl-B-hydroxyglutaric acid by conversion to its bis-(9-bromophenacyl) ester, m.p. 138-141" [Calcd. for C23H2~07Br2. C, 48.44; H, 3.89; Br, 28.03; mol. wt., 570. Found: C, 48.68; H, 4.09: Br, 27.46; mol. wt., 5901 identical with the derivaOH OH OH OH OH tive of an authentic sample2 as shown by the usual The remaining nine carbon fragment of I is repphysical tests. Degradation of I by periodate oxidation followed resented by IV and VII. These must be derived by catalytic reduction and alkaline hydrolysis from a common precursor (VI) which would be exformed three products. One of these was a sodium pected to have two carbonyl and one hydroxyl salt which on acidification gave a lactone (III), oxygen atoms. The bis- (2,4-dinitrophenylhydram.p. 88-88 5" [Calcd. for C,H1201.C, 58.33; H , zone) of VI establishes the presence of two car8.33; C-CH? (21, 20.9; mol. wt , 144. Found: C, bonyl groups. The positive iodoform reaction on 58.27; H, 8.27; C-CH?, 19.9; mol. wt., 144 (sapo%- VI indicates an acetyl or potential acetyl group. if fication equivalent). [ c ~ ] ? ~ -D3 " (C, 2 in metha- The molecular formula for VI1 is that expected nol)]. There was infrared absorption in the 2.9 p in VI there is P-hydroxycarbonyl and 1,4-, 1,5region indicative of hydroxyl and a lactone band at or 1,6-dicarbonyl. The molecular formula for IV 5.82 p . The second product was a neutral liquid coupled with its saturation indicates a tetrahydro(IV), b.p. 37-88' a t 3 mrn [Calcd. for C9Hi80L. furan or tetrahydropyran. The negative iodoform CH3 OH CH3 C, 68.31; H, 11.47; C-CH3 (3), 28.5; mol. wt., I l l 158. Found. C, 68.15; H, 11.39; C-CH?, 23.8; HOOCCH-CH-C€iCOOH + C H ~//O C-CHCHZCH~ mol. w t . , 17G; n?OD 1.4519; [ a I z 6 D + 1 5 " (c, 1 in I methanol) 1. Infrared absorption a t 2.83 p indicated OH hydroxyl. This compound gave a negative iodoI1 form reaction and did not decolorize bromine in CHI CH3 CH3 CHI CH3 CH3 carbon tetrachloride. 3.3-Pentanediol iV).3 b D I I I I /Yo 38" a t 0.05 mm. [Calcd. for C5HizOz C, 57.69; H; C H CH2CHC-CHCHCHCHCH2CH-cHcH~HcH~ + I 11.54. Found c, 57.74; H, 11.78;n Z 51.4402, ~ ' / I I 1 1 I OH OH 011 [CY]% +20" (C, 1 in water)] also was isolated and 0 OHOH OH ~identified by consumption of one mole of periodate per mole and oxidation with bromine to 2,3-peni tanedione whose his- (2,4-dinitrophenylhydrazone + was identical with an authentic sample as shown by C " - ( ) - Z ~ € L the usual physical tests. c H3--\ 0,-c-c H3 IIC € I10 I I Base hydrolysis of dihydroerythronolide followed 1-11 by periodate oxidation formed propionaldehyde, CHI acetic acid, a neutral product (VI) and another acid C H K R z C H O C W I C O O I ~ IV presumably an aldehyde acid. Compound VI gave + a positive iodoform reaction and formed an inC 1 I CH-C' H C H J CH completely purified bis-(2,4-dinitrophenylhydraOH 1 OH 1 yonej, m.p. 235-237" [Calcd. for C21H24iYgOg.N ,
1'
1
.1
4 '
'--I
+
i
(1) P. F. Wiley, K . Gerzon, E. H. Flynn, h l V. Sigal, J r . , a n d U. C. Quaick, THISJ o r r n x . ~ ~ '77, , 3676 ( 1 9 5 5 ) . ( 2 ) S.Reformatski, B P Y . 28, , 32&3 (1895). (3) T h e synthesis of dl-erythro-?,~~(-pentanedil,l hau heen reportmi: J o u R N A r . , 63, see H. .I. l.iicas, h f . J . Schlatter a n d K. C . Jones, THCS 22 (19.41).
?Ha OH
CHa
CH3 I
C) I3 \' I
IL
~
-
CH3
-0
~
I11
+
.-.-Li
3678
Vol. 77
BOOKREVIEWS
reaction of I V indicates the participation of the iodoform reactive group of VI in the cyclization. There are three C-CH3 groups present. These data make structure I V likely for this compound and VI1 most probable for the product of base treatment of VI. The above partial structure contains recurring head to tail units and such a unit seems probable c !I ('
-c
-
throughout and giving structure I for dihydroerythronolide. From previous information regarding the position of desosamine i t can now be placed a t C-3 or C-G in I. The definite placement in erythroinyciii of desosamine, cladinose and the ketonic carbonyl function a t three of the few possible positions (C-3, (2-5. C-6 and C-9) of I reiliains. Evidence conccrniiig these points will be forthcuining. LILLYRESEAKCII
in VI due to the three G C H ! groups prcseiit. 'Thc very logical assumption can be made that VI would fit into I to give a recurring propionate unit
Organic Syntheses. Collective T'olunie 3 . A revised Edition of Annual Volumes 2 - 2 9 . By E . C . HORNING, Editor-in-Chief. John LViley and Sons,Iiic., 440 Fourth Avenue, New York 16, S.Y . 1955. x 890 pp. 16 X 23.5 cm. Price, $15.00. T h e material contained in the auiiual Volumcs of Orgniiic Syntheses 20 through 29 is here collected, edited and revised t o date. Seven new and improved procedures have bceii added. T o bring t h e section 011 Metho
+
1'."~Vl, 1'. \ Y I L E Y /- \V. PI. SEBRELL, J R . , Director, S a tiona! I:i>titutcs of Health, Rethesda, hlarylatid, antl ROBERT S. IIARRIS,Professor of Biocheniistry of Nutrition, Massachusetts Institute of Teclinology, Cambridge. Massachusetts. .katlemic Press, Inc., Publishers, 125 East 23rd Street, Neiv York 10, S.Y . 1954. siii 766 pp. 16.3 X 23.3 c n i . Price, 816.30. T o o\vn this volume (the second of tlirev) a11c.i to be able t o refer to i t for iiifoririatioti concerning the chemistry, physiology anti patholog)- of vitainiris n :tiid K , iiiaciii, pantothenic acid, choline, inositol a n d the essential f a t t y acid. Modern Aspects of Electrochemistry. Etlitetl b y J , O ' p I . \vi11 he most ren.arding. I t is iLutlioritativc, up-to-tlntc, antl ROCKRIS,D.Sc., Ph.D., I>.I.C., I;.I
