Reserpine R 1801 Reference(s): US 2 974 144 (Riker; 7.3.1961 ; appl. 1954; prior. 1953). US 2 876 228 (Pfizer; 3.3.1959; appl. 1956). Klohs, M.W. et al.: J. Am. Chem. Soc. (JACSAT) 77, 2241 (1955). partial synthesis from reserpic acid methyl ester: US 2 854 454 (P. R. Ulshafer; 1958; appl. 1954). Formulation(s): tabl. 0.25 mg, 0.5 mg Trade Name(s): D: Detensitral (Kar1spharma)- comb.; wfrn Diuraupur (Gui1ini)-comb.; wfrn Rauwopur (Giu1ini)-comb.; wfrn F: Aldatense (Sear1e)-comb.; wfm Anaprel F (Servier)-comb.; I: wfm Diviator (Servier)-comb.; J: wfm Sarparel (Servier)-comb.; wfm Tensid (Bayer Pharma)- comb.; wfrn Tensitral (Dausse)-comb.; wfrn Tensitral (SynthC1abo)- comb.; wfrn Resertan (Perkins)-comb.; wfrn Apolon (Toyama) Aporecin (Kay aku) Atension (Santen) Caniramine (Hokuriku) Cinnaloid (Taito Pfizer) Colstamin "Kowa" (Kowa) Daisaloid (Mohan) Isocalsin (Kowa Yakuhin) Rescinate (Ohta) Resiloid (Nippon Shoji) Rozex (Teisan) Sciminan (Kotani) Seripinin (Fuji Zoki) Sinselpin (Kobayashi) USA: Moderil (Pfizer); wfrn Reserpine ATC: C02AA02 Use: antihypertensive, tranquilizer RN: 50-55-5 MF: C3,H4,N,O9 MW: 608.69 EINECS: 200-047-9 LD,,: 21 mgkg (M, i.v.); 200 mglkg (M, p.0.); 15 mgkg (R, i.v.); 420 mglkg (R, p.0.); 500 ~glkg (dog, i.v.) CN: (3P,l6P,l7a,l8P,2Oa)- 1 1 ,I 7-dimethoxy-18-[(3,4,5-trimethoxybenzoy1)oxy Jyohimban- 6-carboxylic acid methyl ester Reserpine By extraction of the roots of Rauwoljia serpentina (L.) Beuth. Reference(s): DE 967 469 (Boehringer Ing.; appl. 1954). US 2 752 351 (Ciba; 1956; appl. 1953). US 2 833 771 (Ciba; 1958; CH-Frior. 1954). US 2 887 489 (Ciba; 1959; CH-prior. 1956). US 2 938 906 (Ciba; 1960; CH-prior. 1952). Dorfmann, L. et al.: Helv. Chim. Acta (HCACAV) 37.59 (1954) Ullmanns Encykl. Tech. Chem., 4. Aufl., Vol. 7, 178. Ullmanns Encykl. Tech. Chem., 3. Aufl., Vol. 13, 277. [oral synthesis: DAS 1 088 062 (Research Corp.; appl. 3.5.1957; USA-prior. 3.5.1956). Hanessian, S et al.: J. Org. Chem. (JOCEAH) 62,465 (1997). Formulation(s): cps. 0.075 mg, 0.15 mg; drg. 0.05 mg, 0.07 mg, 0.1 mg; tabl. 0.1 mg, 0.125 mg, 0.25 mg Trade Name(s): D: Adelphan-Esidrix (Novartis Resaltex (Procter & Pharma)-comb. Gamble)-comb. Barotonal (Brenner-Efeka)- Reserpin I Iameln Serpasil Esidrex (Ciba)- comb.; wfrn combination preparations; comb. (Hameln); wfm wfm Bendigon (Bayer Vital)- Reserpin Saar 1: Brinerdina (Novartis)- comb. Brisarin (Novartis Pharma). comb. Darebon (Novartis Pharma)-comb. Disalpin (ASTA Medica AWD)-comb. Durotan (Beiersdorf-Lilly)- comb. dysto-Loges (Loges)-comb. Modenol (Boehringer Mannh.)-comb. (Chephasaar); wfm Sedaraupin (Boehringer Mannh.); wfrn Serpasil (Ciba); wfrn Triniton (Apogepha)-comb. Tri-Thiazid Reserpin (S tada)-comb. numerous combination preparations F: Tensionorme (Leo)-comb. GB: Abicol (Boots)-comb.; wfm Serpasil (Ciba); wfrn comb. Igroton (Novartis)-comb. J: numerous generic preparations Serpasil (Ciba-Geigy- Takeda) USA: Diupres (Merck Sharp & Dohme)-comb. Diutensen-R (Wallace)- comb. Hydropres (Merck Sharp & Dohme)-comb. Retinol (Axerophthol; Vitamin A) ATC: A I I CAO 1 ; D 1 OAD02; R01 AX02; SO 1XA02 Use: epithehal protective vitamin RN: 68-26-8 MF: C2,H3,0 MW: 286.46 EINECS: 200-683-7 LDSo: 15 10 mgkg (M, p.0.); 2 glkg (R, p.0.) CN: (all-E)-3,7-dimethyl-9-(2,6,6-trimethyl-l-cyclohexen-l-yl)-2,4,6,8-nonatetraen-l-ol acetate RN: 127-47-9 MF: C22H,202 MW: 328.50 EINECS: 204-844-2 LD,,,: 432mglkg (M, 1.v.);4100mg/kg(M,p.o.) propionate RN: 7069-42-3 MF: C2,H,,02 MW: 342.52 EINECS: 230-363-2 palmitate RN: 79-81-2 MF: C3,H6,O2 MW: 524.87 EINECS: 201-228-5 LDo; 6060 mgkg (M, p.0.); 7910 mgkg (R, p.0.) acetylene (1) ketane 3-hydroxy-3- methyl-1 - penten-4-yne Retinol R 1803 p-ionone (1V) ethyl chloroacetote ti , Pd-Pb Z VI Lindlar catalyst 'aldehyde C1/ (V) ocetyl chloride (VII) retinol acetote (M) 1 Retinol w 0 jH3 + HO\~O~CH~ - OHC dibutyl- H ,C/O amine propion- ethyl hydroxy- ethyl 3-formyl- aldehyde methoxyocetate crotonote (X) H~CV~'$&H + YII HZO, H+ OHC EOicHT 4,4-diethoxy-3-methyl- crotyl alcohol (XI) 3-formylcrotyl acetate (XI) 1804 R Retinol alternative synthesis: Na. liq. NH, IV +I - vinyl-@-ion01 (XIV) c1- NoOCH, , Xv triphenyl- phosphine @ A. E. c.: HO CH, (XVII) . HCI IV + H3C\O/CH0 methyl formote (XVI) 4 "l l" uCH, 'ct (m11) methylmagnesium bromide (XR) Retinol R 1805 1. XVI. NaOCY H3C CH, CH3 H~CP~; 2. XVII. HCI WHO + H3C -xx' CH3 F-ionylidene- acetone acetaldehyde (XX) H,C CH, CH3 CH3 ~CHO 'OBH4 , retinal @ Rhone-Poulenc: PNo H3C CH, CH3 3-methyl-2-but~ne sodium phenylsulfinate 1. KOH, CZHSOH O=S=O 2. KOCH3 - CsH5S02K (mo Retinol polrnitate: methyl palmitate Retinol palmitate Referencefs): reviews: Isler, 0.; Brubacher, G.: Vitamine I (Fat SolubleVitamins), Thieme Verlag Stuttgart, New York 1982. Ullmann's Encyclopedia of Industrial Chemistry, 5th Ed., Vol. A27, p. 453-469, VCH Verlagsges. m.b.H., Weinheim 1996. 1806 R Retinol older review: Baxter, J.G.: Fortschr. Chem. Org. Naturst. (FCONAA) 9, 41 (1952). a Isler, 0. et a].: Helv. Chim. Acta (HCACAV) 30, 191 1 (1947). Isler, 0. et a].: Helv. Chim. Acta (HCACAV) 32, 489 (1949). Isler, 0.: Chirnia (CHIMAD) 4, 103 (1950). Isler, 0.: Angew. Chem. (ANCEAD) 68,547 (1956). DE 839 495 (Roche; appl. 1949; CH-prior. 1945, 1947). DE 844 596 (Roche; appl. 1949; CH-prior. 1947). DE 842 190 (Roche; appl. 1949; CH-prior. 1946) ("C,,-aldehyde") b Pommer, H.: Angcw. Chem. (ANCEAD) 72,811,911 (1 960). Pommer, H.: Angew. Chem. (ANCEAD) 89,437 (1977). Reif, W.; Grassner, H.: Chern 1ng Tech. (CITEAH) 45,646 (1973). Freyschlag, H. el al.: Angew. Chem. (ANCEAD) 77,277 (1965). DE 957 942 (BASF; appl. 1955). DE 1 059 900 (BASF; appl. 1957). DE 1 060 386 (BASF; appl. 1957). DE 1 068 702 (BASF; appl. 1958). ethinylation ofp-ionone: DE 1 081 883 (BASF; appl. 1958). synthesis of 3-formylcrotyl acetate: DAS 2 004 675 (BASF; appl. 1970). EP 87 097 (BASF; appl. 14.2.1983; D-prior. 20.2.1982). c FR 1 243 824 (A.E.C.). d Julia, M.; Arnould, D.: Bull. Soc. Chim. Fr. (BSCFAS) 1973,743,746 DOS 2 305 267 (RhGne-Poulenc). DAS 2 361 144 (RhGne-Poulenc; appl. 7.12.1973; F-prior. 7.12.1972,22.12.1972). DE 2 734 172 (RhSne-Poulenc; appl. 28.7.1977; F-prior. 28.7.1976). Formulation(s): cps. 2500 iu, 30000 iu, 50000 iu; drg. 10000 iu (as acetate); drops 1000 idml, I0000 iulg, 40000 iulml; cmulsion 30000 iulml, 300000 idg; gel 1000 iulml; ointment 250 iulg, 10000 iulg; tabl. 20000 iu. Trade Name(s): D: A-Mulsin (Mucos) Arovit (Roche); wfm A-Vicotrat (Heyl) F: Oculotect Augentropfen (CIBA Vision) Ophlosan Augentropfen (Winzer) Retinol (Ursapharm) Solan (Winzer) Taxofit Vitamin A (Anasco); wfm Vitamin A Dispersa (CIBA Vision) GR: Vitamin A Dispersa Baeschlin (Baeschlin); wfm Vitamin-A-Kapseln "Extracta" (Extracta); wfm Vitamin-A-POS (Ursapharm) I: Vitamin- A-Saar (Chephasaar) Vogan (Merck); wfm generics and circa 300 combination preparations A 313 (Pharmadtveloppement) Arovit Roche (Roche) Avibon (ThCraplix) Halivi te (Whitehall) Vitamine A Dulcis (Allergan) Vitamine A Faure (ThBa) numerous combination preparations Abidec (Warncr-Lambert)- comb. Dalivit drops (Eastern)- comb. numerous combination preparations AD Pabyrn (Sami1)-comb. Adisterolo (Abiogen Pharma)-comb. Arovit (Roche) Euvitol (Bracco) Euvltol Labra (Bracco) Evitex (Alcon) Haliborange (Eurospital)- comb. Lasonil H Antiemon: (Bayer)-comb. Midium (Teofarma)-comb. Repervit (IDI) Rovigon (Roche)-comb. Tocalfa (ASTA Medics)- comb. Vitalipid (Pharmacia & Upjohn) J: numerous combination preparations USA: ACES (Carlson)-comb. Aquasol A (Astra) Lazer (Pedino1)-comb. Matema (Lederle)-comb. Megadose (Arco)-comb. Vi-Daylin (Ross)-comb. Ribavirin R 1807 - Ribavirin ATC: JO~ABO~ Use: antiviral RN: 36791-04-5 MF: C,H,,N,O, MW: 244.21 LD,,: 2700 mgkg (R, p.0.) CN: 1-0-D-ribofuranosyl- 1 H- 1,2,4-triazole-3-carboxamide methyl 1,2,3,5-tetra-0-acetyl- 1,2,4-triazole- 8-0-ribofuranose 3-carboxylote OH OH Ribovirin methyl 1 -(2,3,5-tri-0- acetyl-8-D-ribofuranosy1)- 1,2.4-triorole-3-carboxylate (I) ~itkowski, J.T.: J. Med. Chem. (JMCMAR) 15, 1150 (1972). alternative syntheses: DOS 2 220 246 (ICN; appl. 25.4.1972; USA-prior. 1.6.1971,31.3.1972). DOS 2 441 823 (ICN; appl. 12.3.1974; USA-prior. 12.3.1973). DOS 2 51 1 828 (ICN; appl. 18.3.1975; USA-prior. 18.3.1974). JP-appl. 75 123 883 (Kyowa; appl. 15.3.1974). US 3 976 545 (ICN; 24.8.1976; prior. 1.6.1971). US 4 138 547 (ICN; 6.2.1979; prior. 22.12.1977). structure and conformation: Kreishman, G.P. et al.: J. Am. Chem. Soc. (JACSAT) 94, 5894 (1972). Formulation(s): powder 6 g (for preparation of inhalation solution) Trade Name(s): D: Virazole (ICN) I: Viramid (Alfa USA: Virazole (ICN) Wassermann) Riboflavin (Lactoflavin; Vitamin B,) ATC: A1 1HA04 Use: vitamin RN: 83-88-5 MF: C,,H,,N,O, MW: 376.37 EINECS: 201-507-1 LD,,,: 50 mglkg (R, i.v.); 110 glkg (R, p.0.) CN: 1-deoxy-1-[3,4-dihydro-7,8-dimethyl-2,4-dioxobenzo[g]pteridin- lO(2H)-yl]-D-ribitol 1808 R Riboflavin 5'-phosphate munosodium salt RN: 130-40-5 MF: C,,H,,N,NaO,P MW: 478.33 N-(3.4-dimethylpheny1)-D-ribomlne OH H H,. Raney-Ni ti + CHO F H 3,4-dimethyl- D- ribose aniline (I) D-ribonic acid loctone ribofiovin benzenediazonium chloride dithionite N-(3.4-dimethyl- ~hen~l)-D- ribamine (11) * CH2 0 H~C,AAH borbituric HO r :fYH H FH2 0 Riboflavin Riboflavin a Re ference(s): a IJS 2 384 105 (Roche; 1945; appl. 1943). b US 2 41 1 61 1 (Roche; 1946; GB-prior. 1941). US 2 422 997 (Roche; 1947; appl. 1944). DAS 2 558 515 (BASF; appl. 24.12.1975) -hydrogenation on Cu-Cr,O,. DAS 2 558 5 16 (BASF; appl. 24.1 2.1975) - hydrogenation on Cu- Cr203. F Riboflavin R 1809 alternative syntheses (from 3,4-dimethylnitrobenzene): DOS 2 650 830 (BASF; appl. 6.11.1976). c Tishler, M. et al.: J. Am. Chem. Soc. (JACSAT) 69, 1487 (1947). US 2 350 376 (Merck & Co.; 1944; appl. 1941). US 2 370 093 (Merck & Co.; 1945; appl. 1941). similar processes: Tishler, M. et al.: J. Am. Chem. Soc. (JACSAT) 67, 2165 (1945). US 2 807 61 1 (Merck & Co.; 1957; appl. 1955). d Karrer, P.; Meerwein, H.: Helv. Chim. Acta (HCACAV) 18, 1130 (1935). Kuhn, R.; Weygand, F.: Ber. Dtsch. Chem. Ges. (BDCGAS) 68,1282 (1935). fermentative methods: US 2 445 128 (USA-Secret. Agriculture, 1948; Anm, 1946). US 2483 855 (Commercial Solvents Corp.; 1949; appl. 1942). US 2 876 169 (Grain Process. Corp.; 1959; appl. 1956). US 4 165 250 (Merck & Co.; 21.8.1979; prior. 29.8.1975, 22.3.1976, 14.1 1.1977)) isolation from fermentation liquors andpur~jication: US 2 387 023 (Commercial Solvents Corp.; 1945; appl. 1944). US 2 421 142 (Commercial Solvents Corp.; 1947; appl. 1944). US 2 367 646 (Commercial Solvents Corp.; 1945; appl. 1943). US 2 571 896 (Merck & Co.; 195 1; appl. 1945). US 2 797 215 (Commercial Solvents Corp.; 1957; prior. 1951, 1955). US 4 165 250 (Merck & Co.; 21.8.1979; prior. 29.8.1975, 22.3.1976, 14.1 1.1977). Formulation(s): amp. 10 mg/2 ml, 20 mglml (as 5'-phosphate monosodium salt); drg. 10 mg; tabl. 10 mg Trade Name(s): D: Biovital (Dr. Schieffer)- comb. B-Komplex-Vicotrat (Heyl) BVK Rochc (Roche Nicholas) Doppelherz (Quiesser Pharma) Eunova (SmithKline Bcecham OTC Medicines) Kendural (Abbott) Merz Spezial Dragees (Merz & Co.) - Multibionta (Merck Produkte) Multi Sanostol (Roland) Polybion (Merck) Tai Ginseng (Dr. Poehlmann) Vita Buerlecithin (Roland)- comb. and circa 300 combination preparations F: Alvityl (Solvay Pharma)- comb. B-Chabre (ATC Pharma)- comb. Bkcozyme (Roche)-comb. Beflavine (Roche) Capsules Pharmaton (Boehringer 1ng.)-comb. Carencyl (Riomj-comb. Glutamag Vitamink (Euform)-comb. Hydrosol polyvitamink Labaz (Labaz)-comb. Hydrosol polyvitamink Roche (Roche)-comb. Nutrighe (GNR-pharma)- comb. Plurifactor (Gomeno1)- comb. Renutryl 500 (Nest16 clinical)-comb. Survitine (Roche Nicholas)-comb. Vitamine C-B, Lemoine (Lemoine)-comb. Vivamyne (Whitehall) comb. numerous combination preparations GB: only combination preparations: Abidec (Warner-Lamben) Dalivit Drops (Paines & Byme) Ketovite (Paines & Byrne) Pabrinex (Link) I: following vitaminous combination preparations: Becozym (Roche) Berocca (Roche) Betacomplesso (Medosan) Betotal (Pharmacia & Upjohn) Diagran (Bristol-Myers Squibb) Emazian (Bioindustria) Emoantitossina (Piam) Idropan B (Lisapharma) Idroplurivit (Menarini) Ipav~t (IPA) Katabios (SIT) Neocromaton (Menarini) Plexoton B 12 (Coli) Priovit (SIT) Sincrivlt (AGIPS) Vinutro Drops (Bergamon) Vitalerina (Polifarma) Vitamax (Medosan) Vitate (SIT) Viterra (Pfizer) J: numerous combination preparations IJSA: Mega-B (Arco) 1810 R Ribostamycin Ribostamycin (Rihostamin) ATC: JOlCBlO Use: antibiotic RN: 25546-65-0 MF: C,,H,,N4010 MW: 454.48 EINECS: 247-091-5 LD,,: 300 mglkg (M, i.v.); 7 glkg (M, p.0.); 535 mg/kg (R, i.v.); >10 glkg (R, p.0.) CN: 0-2,6-diamino-2,6-dideoxy-a-~-glucopyranosyl(1+4)-0-[~-~-ribofuranosyl-(l+5)]-2-deoxy-~- streptamine sulfate RN: 53797-35-6 MF: C,,H,,N,O,, . xH,S04 MW: unspecified EINECS: 258-783-1 LD,,: 210 mg/kg (M, i.v.); >7 gkg (M, p.0.); 375 mgkg (R, i.v.); >7 g/kg (R, p.0.) by ferrnentotion from Streptomyces ribosidicus (ATCC 21294) 4-0-r2.6-bis(benzyloxycorbonyl- 2.3.5-tri-0-benzyl- omino)3.4-di-O-benzyl-2,6-di- 6-D-ribofuranosyl deoxy-u-D-glucapyronosyl]-N,N'- chloride bis(benzyloxycorbcnyl)-2-deoxy- D-streptarnine 1. NoOCH, 2. H,, Pd-C ____, Hq(CN),. CoSO,. CHCI, + 1 rnercury(l1) cyanide a DE 1 814 735 (Meiji Seika Kaisha; appl. 14.12.1968; J-prior. 15.10.1968, 18.12.1967). Shomura, T. et al.: J. Antibiot. (JANTAJ) 23, 155 (1970). US 3 661 892 (Meiji Seika; appl. 3.12.1968; J-prior. 18.12.1967). US 3 799 842 (Meiji Seika; USA-prior. 1.6.1970; J-prior. 15.10.1968, 18.12.1967). b DOS 2 104 129 (Meiji Seika Kaisha; appl. 29.1.1971; J-prior. 2.2.1970). . 21294) 4-0 -r2.6-bis(benzyloxycorbonyl- 2.3.5-tri-0-benzyl- omino)3.4-di-O-benzyl-2,6-di- 6-D-ribofuranosyl deoxy-u-D-glucapyronosyl]-N,N&apos ;- chloride bis(benzyloxycorbcnyl )-2 -deoxy- D-streptarnine. CN: 0-2 ,6-diamino-2,6-dideoxy-a-~-glucopyranosyl(1+4 )-0 -[ ~-~ -ribofuranosyl-(l+5) ]-2 -deoxy- ~- streptamine sulfate RN: 5379 7-3 5-6 MF: C,,H,,N,O,, . xH,S04 MW: unspecified EINECS: 25 8-7 8 3-1 LD,,:. 3679 1-0 4-5 MF: C,H,,N,O, MW: 244.21 LD,,: 2700 mgkg (R, p.0.) CN: 1-0 -D-ribofuranosyl- 1 H- 1,2,4-triazole-3-carboxamide methyl 1,2,3,5-tetra-0-acetyl- 1,2,4-triazole- 8-0 -ribofuranose 3-carboxylote