Fig. 1 illustrates a definition of the terms endocyclic and exocyclic SN‐reactions, referring to intramolecular nucleophilic substitution processes that occur by an SN2‐analogous mechanism. Crossing experiments show that the methyl transfer I → II (see scheme 1) does not follow the formally appealing mechanism of the endocyclic SN‐process III; the reaction proceeds intermolecularly under all conditions investigated. Kinetic measurements indicate that the methyl transfer XI → XII (see scheme 3) occurs in a similar fashion. This behaviour is believed to follow from the preference of tetrahedral carbon for backside attack by the nucleophile in SN2‐reactions. The general experience, according to which intramolecular reaction paths over cyclic transition states with ring sizes of 5 or 6 are preferred to their intermolecular counterparts, is not to be extrapolated to SN2‐reactions at tetrahedral carbon.

Phytochemical analysis of the dichloromethane:methanol (1∶1) extract of root parts of Prangos pabularia led to the isolation of twelve cytotoxic constituents, viz., 6-hydroxycoumarin (1), 7-hydroxycoumarin (2), heraclenol-glycoside (3), xanthotoxol (4), heraclenol (5), oxypeucedanin hydrate (6), 8-((3,3-dimethyloxiran-2-yl)methyl)-7-methoxy-2H-chromen-2-one (7), oxypeucedanin hydrate monoacetate (8), xanthotoxin (9), 4-((2-hydroxy-3-methylbut-3-en-1-yl)oxy)-7H-furo[3,2-g]chromen-7-one (10), imperatorin (11) and osthol (12). The isolates were identified using spectral techniques in the light of literature. 3-(4,5-dimethyl thiazol-2yl)-2,5-diphenyltetrazolium bromide (MTT) cytotoxicity screening of the isolated constituents was carried out against six human cancer cell lines including lung (A549 and NCI-H322), epidermoid carcinoma (A431), melanoma (A375), prostate (PC-3) and Colon (HCT-116) cell lines. Osthol (12) exhibited the highest cytotoxicity with IC50 values of 3.2, 6.2, 10.9, 14.5, 24.8, and 30.2 µM against epidermoid carcinoma (A431), melanoma (A375), lung (NCI-H322), lung (A549), prostate (PC-3) and colon (HCT-116) cell lines respectively. Epidermoid carcinoma cell line A431 was sensitive to most of the compounds followed by lung (A549) cancer cell line. Finally a simple and reliable HPLC method was developed (RP-HPLC-DAD) and validated for the simultaneous quantification of these cytotoxic constituents in Prangos pabularia. The extract was analyzed using a reversed-phase Agilent ZORBAX eclipse plus column C18 (4.6×250 mm, 5 µm) at 250 nm wavelength using a gradient water-methanol solvent system at a flow rate of 0.8 ml/min. The RP-HPLC method is validated in terms of recovery, linearity, accuracy and precision (intra and inter-day validation). This method, because of shorter analysis time, makes it valuable for the commercial quality control of Prangos pabularia extracts and its future pharmaceutical preparations.

Corphin derivatives synthesized earlier in our laboratory have been used for the preparation of tetrahydro-and hexahydrocorphinoid nickel(I1)-complexes containing novel chromophore systems. The UV./VIS. and IHand '3C-NMR. spectral data of these complexes were relevant to the structure determination of Factor F430 described in the following paper.Vor mehr als einem Jahrzehnt wurden in unserem Laboratorium Vertreter des Corphin-Ligandsystems synthetisiert [2-715) (vgl. Schema Z). Jene Synthesen waren durch die aus damaliger corrinchemischer Sicht attraktive Vermutung ausgelost worden, dass dieses his dahin unbekannte porphinisch-corrinische Ligandsystem eine Rolle bei der Biosynthese des Corrinkerns von Vitamin B,, spielen konnte. Gezielte Versuche zur Auffindung einer entsprechenden reduktiven Corphin -+ Corrin-Ringkontraktion bei Modell-Corphinderivaten des Typs 2 sind dann allerdings erfolglos geblieben. Die wichtige (und damals uberraschende) Entdeckung von Shemin [I 11 und Scott [12] aus dem Jahre 1972, wonach bei der Biosynthese des Vitamins B,, das Uroporphyrinogen(lI1)-meso-C-Atom zwischen den Ringen A und D auf dem Wege von Uroporphyrinogen(II1) zur Cobyrsaure nicht zum C-Atom der angularen Methylgruppe am Ring A des Corrinsystems wird, sondern vielmehr verloren geht, hat dann das Interesse am Strukturtyp der Corphine zeitweilig in den I ) 2)3, 4, )Diese Mitteilung enthalt u. a. Ergebnisse aus den Dissertationen von A . Fussler[l] und P. M. Miilfer[2], wo sich auch weitere experimentelle Angaben finden. Doktorat ETHZ 1969-73;~.

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