0012-5008/03/0007- $25.00 © 2003 åÄIä “Nauka /Interperiodica” 0188 Doklady Chemistry, Vol. 391, Nos. 1–3, 2003, pp. 188–190. Translated from Doklady Akademii Nauk, Vol. 391, No. 3, 2003, pp. 346–348. Original Russian Text Copyright © 2003 by Odinokov, Spivak, Nazarova, Mallyabaeva, Emel’yanova, Krysin, Dzhemilev. The role of vitamin ä 1 in various biochemical pro- cesses (blood coagulation, conjugate oxidation and phosphorylation) is caused to a great extent by its cyclic chroman form—2,5-dimethyl-2-(4,8,12-trime- thyltridec-1-yl)-6-hydroxybenzo[h]chroman—named chromanol of vitamin ä 1 or naphthotocopherol [1]. Naphthotocopherol was identified in the product of enzymatic reduction of vitamin ä 1 [2]. Recent spectrophotometric study of the antioxi- dant activity of the compounds of a phenol series showed naphthotocopherol to have the highest anti- oxidant activity among the known phenol antioxi- dants, including α-tocopherol, whose activity was 6.9 times lower [3]. One should expect naphthotoco- pherol to show a high antioxidant activity in vivo due to the presence of the phytyl side chain, which pro- vides transport of the antioxidant across the biologi- cal membrane of a cell. Naphthotocopherol in all–rac form (a mixture of eight stereoisomers) has been synthesized by the acid-catalyzed condensation of 2-methyl-1,4-naph- thohydroquinone (menadiol) with racemic isophytol in the presence of concentrated mineral acids (HCl, H 2 SO 4 ) or such a strong condensing agent as ZnCl 2 , as well as by the reductive cyclization of vitamin ä 1 under the action of SnCl 2 and concentrated HCl [3, 4]. Here, we synthesized, for the first time, optically active naphthotocopherol with a stereochemically homogeneous (R,R) configuration of the phytyl side chain (VI). The synthesis is based on the use of (R,R)-phyton obtained by the ozonolysis of acetone extract of chlorophyll from great nettle (Urtica dio- ica L.) [5]. Natural (R,R)-phyton (II) converted by vinylation into (3RS,7R,11R)-isophytol (III) was involved in condensation with 1-O-acetyl-2-methyl- 1,4-naphthohydroquinone (IV) under catalysis by zeolite-containing aluminosilicate Zeokar-10 fol- lowed by the deacetylation of the condensation prod- uct (V) by treatment with lithium aluminum hydride in diethyl ether. The yield of target naphthotoco- pherol VI was 68% in terms of isophytol III. It should be noted that the use of aluminosilicates (AShNTs-3, Zeokar-2) in the condensation of isophy- tol III with menadiol acetate IV was previously reported in [6, 7]. However, the reaction led to the monoacetate of 1,4-dihydro derivative of vitamin ä 1 , whose prolonged heating resulted in the correspond- ing diaryl ether (instead of cyclization) [6]. The structure of acetate V is assigned on the basis of IR, UV, and 1 H and 13 C NMR spectra. Thus, the 2,2-disubstituted chroman structure of compound V is characterized by the signal of the C-2 atom at δ 75.6 ppm ( 13 C NMR spectrum) and the triplet sig- nal at δ 2.76 ppm ( 1 H NMR spectrum) typical of the ç 2 ë 4 group bound to the aromatic ring [8]. Chroman V is a 1 : 1 mixture of two diastereomers with (2R, 4' R, 8' R) and (2S, 4' R, 8' R) configurations, which is sup- ported by the presence of two singlets of equal inten- sity in the 1 H NMR spectrum (δ 1.35 and 1.40 ppm), corresponding to the ëç 3 groups at the racemic chiral center C-2. The presence of the racemic C-2 atom leads to the appearance of a double set of 13 C NMR signals for C-4 (δ 20.59 and 21.00 ppm) and C-1' (δ 39.99 and 40.06 ppm), similar to the spectral pattern previously observed for 2-ambo-α- tocopherol [5]. The high-resolution mass spectrum of acetate V contains [å] + peak (m/z 494) with a rel- ative intensity of 34%, while the [M-COCH 2 ] + ion with m/z 452 gives rise to the highest peak. CHEMISTRY Synthesis of Cyclic Chroman Form of Vitamin K 1 with Side Chain of Stereochemically Homogeneous (R,R) Configuration V. N. Odinokov, A. Yu. Spivak, O. V. Nazarova, M. I. Mallyabaeva, G. A. Emel’yanova, A. P. Krysin, and Corresponding Member of the RAS U. M. Dzhemilev Received March 28, 2003 Institute of Petroleum Chemistry and Catalysis, Academy of Sciences of Bashkortostan and Ufa Research Center, Russian Academy of Sciences, pr. Oktyabrya 141, Ufa, 450075 Russia