piperidines and dihydropinidine

The 2,6-disubstituted piperidine alkaloids (+)-dihydropinidine (1), (-)-epidihydropinidine (2) (as HCl salts), and (-)-pinidinone (3) were efficiently synthesized from (S)-epichlorohydrin (7) as common substrate using regioselective Wacker-Tsuji oxidation of alkenylazides 10 and 14 as well as a highly diastereoselective reduction of cyclic imine 11 as key steps. The protecting group free total syntheses represent the up to date shortest routes with highest overall yields for all three naturally occurring alkaloids (1-3). The first single-crystal X-ray analysis of (-)-epidihydropinidine hydrochloride (2·HCl) confirmed its proposed absolute configuration to be (2S,6S), corresponding to that of the isolated natural product.

Topics: Alkaloids; Molecular Structure; Picea; Pinus; Piperidines; Stereoisomerism

[reaction: see text] A stepwise [3+3] annelation sequence to tetrahydropyridines via addition of the Büchi Grignard to aziridines has been developed. These intermediates can be further functionalized with good regio- and stereocontrol and this methodology has been employed in the stereoselective formal synthesis of (-)-dihydropinidine.

Topics: Catalysis; Molecular Structure; Piperidines; Pyridines; Stereoisomerism

Total syntheses of enantiopure alkaloidal natural products (2S,6R)-dihydropinidine (as hydrochloride) and (2S,6R)-isosolenopsins (as hydrochlorides) were achieved in four steps and in 80-82% total yields by using a synthetic strategy of the formation-cleavage of 1,3-oxazinane. (S)-Betti base was proved to be an excellent chiral auxiliary and a novel Pd/C catalyzed N-debenzylation straightforward to amine hydrochloride was developed in the presence of CH2Cl2.

Topics: Alkaloids; Molecular Conformation; Piperidines; Stereoisomerism

(+) and (-)-Dihydropinidine and (+)- and (-)-epidihydropinidine were synthesized from hydroxy esters 1 and 2 which had been prepared by yeast reduction of methyl (2-oxocyclohexyl)acetate. The enantiomeric excess at the C-1 positions of 1 and 2 were both determined as more than 99% ee.

Topics: Acetates; Cyclohexanones; Molecular Structure; Oxidation-Reduction; Piperidines; Saccharomyces cerevisiae

A conceptually new approach to the enantiocontrolled synthesis of 2,6-disubstituted piperidines was achieved by desymmetrization of meso-2,6-dimethoxy-eta-(3,4,5)-dihydropyridinylmolybdenum complexes. After protection of the piperidine nitrogen as a urethane derived from (+)- or (-)-trans-2-(alpha-cumyl)cyclohexyl (TCC), a sequential, one-pot methoxide abstraction/nucleophilic addition/methoxide abstraction/nucleophilic addition generated good yields of 2,6-disubstituted-eta-(3,4,5)-dihydropyridinylmolybdenum complexes. This sequence proceeds by way of a highly diastereoselective methoxide abstraction (>40:1). High yielding protodemetalation and N-deprotection provided a simple and enantiocontrolled synthetic entry to a variety of 2,6-disubstituted piperidines. This new method was used for the total synthesis of (-)-dihydropinidine and (-)-andrachcinidine.

Topics: Alkaloids; Dihydropyridines; Molybdenum; Organometallic Compounds; Piperidines; Stereoisomerism

To estimate the prevalence, awareness, treatment and control of hypertension in a Canarian population; and their relationship with the glucose tolerance categories.. From a population of 6355 subjects over 29 years old, 690 were chosen in a random sampling. Blood pressure measurements, a standard oral glucose tolerance test (excluding known diabetic patients), and a questionnaire on diabetes and hypertension history and medication use was performed.. The total prevalence of hypertension was 50.3%; 62.0% of the hypertensive subjects were aware of their condition; 60.6% had their diastolic and 11.0% their systolic blood pressure controlled and 8.6% had both. For diabetic, glucose intolerant and normoglycemic subjects, the respective prevalences of hypertension were 79.4, 60.2 and 43.1% (higher in diabetic subjects, P < 0.001); the awareness of hypertension was 66.7, 61.8 and 59.5% (differences not significant); systolic blood pressure control was 4.8, 14.7 and 13.7% (lower in diabetic subjects, P = 0.017 versus glucose intolerant and P = 0.011 versus normoglycemic subjects); diastolic blood pressure control was 50.4, 72.1 and 63.2% (lower in diabetic subjects, P = 0.004 versus glucose intolerant and P = 0.025 versus normoglycemic subjects). There were no differences in the number and type of antihypertensive drugs among the different glucose tolerance categories.. Blood pressure was comparable in our population and in other European populations. The prevalence of hypertension was higher, the awareness was similar, and control was worse in diabetic than in non-diabetic subjects; the drug treatment pattern was not different.

Topics: Adrenergic alpha-Antagonists; Adrenergic beta-Antagonists; Adult; Aged; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Awareness; Blood Pressure; Calcium Channel Blockers; Diabetes Mellitus; Diastole; Diuretics; Drug Therapy, Combination; Female; Glucose Intolerance; Humans; Hypertension; Male; Middle Aged; Piperidines; Prevalence; Spain; Systole; Treatment Outcome

[reaction: see text] Sequences of lithiation-substitution, enantioselective hydrogenation, and diastereoselective lithiation-substitution provide efficient highly enantioselective syntheses of 2-substituted and cis and trans 2,6-disubstituted piperidines. The methodology is demonstrated by syntheses of (-)-coniine, (-)-solenopsin A, and (-)-dihydropinidine as their hydrochlorides.

Topics: Alkaloids; Analgesics; Piperidines; Stereoisomerism