Reaction of rac-H-3 with (−)-ethyl isocyanate permitted isolation by crystallization of one of the two diastereomeric urea derivatives formed (the other does not crystallize). Reaction with the Grignard reagent of propargyl iodide gave racemic propargyl indolenine rac-H-2; ring closure to the aminoketone rac-H-3 was brought about by BF3 and HgO in MeOH through intermediate rac-H-2a (electrophilic addition) with the two methyl groups forced into a cis-relationship by kinetic as well as thermodynamic reasons. Resolution of the racemic aminoketone into the two enantiomers. H-3. For this determination, the levo-rotatory ("unnatural") enantiomer of aminoketone (−)-H-3 was used in order to save precious material: Acylation of the amino group of (−)-H-3 with chloroacetyl chloride, followed by treatment of the product H-3a with potassium t-butoxide in t-butanol, afforded tetracyclic keto-lactame H-3b. 524-525 The "unnatural" (−)-enantiomer (−)-H-3 was used to determine the absolute configuration; in various later steps, (−)-H-3 and enantio-intermediates derived from it were used as model compounds in exploratory experiments. The A-D-component was synthesized at Harvard from a ring-A precursor (prepared from achiral starting materials), and a ring-D precursor prepared from (−)-camphor. Reduction of the aldehyde group with NaBH4 to H-33, mesylation of the primary hydroxy group with methanesulfonic anhydride under conditions that also convert the primary amide group into the desired nitrile group and, finally, replacement of the methansulfonyloxy group by bromide produced A-D-component H-34 with the propionic acid function at ring D as nitrile, differentiated from all other such side chains.
Th is conte nt h as been done with the help of GSA Con tent Gen erator Dem over sion.
H-30u. Ozonolysis to aldehyde H-32u, reduction of the aldehyde group with NaBH4 in MeOH to the primary alcohol H-33u and, finally, conversion of the hydroxy group via the corresponding mesylate gave bromide H-34u. 538-539 containing the carboxyl function of the ring D propionic acid side chain as a nitrile group, differentiated from all the other methoxycarbonyl groups, involved the following steps: treatment of H-29 with a methanolic solution of thiophenol and HCl afforded phenyl-thioenolether derivative H-30, which upon ozonolysis at low temperature gave the corresponding thioester-aldehyde H-31 and, when followed by treatment with liquid ammonia, the amide H-32. It was fortunate indeed that, just around that time, the technique of high pressure liquid chromatography (HPLC) had been developed in analytical chemistry. Birch reduction of H-20 (lithium in liquid ammonia, t-butanol, THF) provided tetraene H-21. In anticipation of the Birch reduction of the aromatic ring, protective groups for the two carbonyl functions of H-16 were required, one for the ketone carbonyl group as ketal H-17, and the other for https://www.amazon.com/Vitamin-Gummies-Delicious-Vitamins-Support/dp/B08BW6JLH4/ the lactam carbonyl as the highly sensitive enol ether H-20. Vitamin B12 is a key nutrient that your body needs for many essential functions. The final conversion of the common corrinoid intermediate 2 (fig. 6) from the two approaches into the target cobyric acid required the introduction of the two missing methyl groups at the meso positions of the corrin chromophore between rings A/B and C/D, as well as the conversion of all peripheral carboxyl functions into their amide form, except the critical carboxyl at the ring-D f-side chain (see fig. 6). These steps were collaboratively explored in strictly parallel fashion in both laboratories, the Harvard group using material produced via the A/B approach, the ETH group such prepared by the photochemical A/D approach. Data w as c reated wi th GSA Content Generator DEMO .
This is the oxime of the sterically more hindered ketone group, the nitrogen atom of which is destined to become the nitrogen of the target molecule's ring D. Crucial for this purpose is the configuration at the monoxime double bond, the hydroxyl group occupying the sterically less hindered position. H-25. An intramolecular aldol condensation of the 1,5-dicarbonyl unit in MeOH using pyrrolidine acetate as the base, followed by tosylation of the oxime's hydroxyl group, afforded the cyclohexenone derivative H-26. Equilibration of α-corrnorsterone H-28 by heating in strong base, followed by acidification and treatment with diazomethane, led to the isolation of pure β-corrnorsterone H-29 in 90 % yield. This compound required strongly alkaline conditions in order to open its lactam ring, but it was discovered that a minor isomer, also isolated from the reaction mixture, β-corrnorsterone H-29, undergoes this lactam ring opening under alkaline condition with great ease. Conversion of its N-nitroso derivative H-7 gave diazo compound H-8. Thermal decomposition of H-8 induced methyl migration to give cyclopentene H-9.
This constitutes the model A-D-component, the one with an undifferentiated propionic acid function at ring D (i.e., bearing a methyl ester group like all other side chains). A model A-D-component was used to explore the coupling conditions; this component differed from the A-D-component used in the final synthesis by having as the functional group at the ring-D f-side chain a methyl ester group (like all other side chains) instead of a nitrile group. Reduction to H-10 (LiAlH4), oxidation (chromic acid) to aldehyde H-11, Wittig reaction (carbomethoxymethylenetriphenylphosphorane) to H-12 and hydrolysis of the ester group finally gave trans-carboxylic acid H-13. The ethylene ketal protecting group in pentacyclenone H-22 was converted to the ketone group of H-23 by acid-catalyzed hydrolysis. Its keto carbonyl was converted to a methylene group by desulfurization of the dithioketal of H-3b with Raney nickel to give lactam H-3c. H-3f. When treated with potassium t-butoxide in t-butanol and subsequently with KOH, H-3f was converted to H-3h, clearly by way of the intermediate H-3g.