Synthesis of therapeutic and diagnostic drugs centered on regioselective and stereoselective ring opening of aziridinium ions

A method of stereoselective or regioselective synthesis through ring opening of aziridinium ions, comprising:

• converting a substituted β amino alcohol to a substituted alkylating agent, wherein the substituted alkylating agent is a substituted β-amino halide comprising:
• converting the substituted alkylating agent in the presence of halosequestering agent comprising AgClO4, AgOTf, Ag2CO3, AgOTs, AgNO3, AgSbF6, or AgBF4 to a substituted aziridinium ion selected from:
• where:
• Y is a non-nucleophilic counter anion or a leaving group comprising halide, perchlorate, tetrafluoroborate, hexafluoroantimonate, mesylate, triflate, carbonate, nitrate, phthalimide, or succinimide;
• each of R1-4 independently is hydrogen, carboxyalkyl, alkylamido, alkyl, allyl, benzyl, benzyloxyalkyl, cycloalkyl, heterocyclyl, alkoxy, hydroxyalkyl, aryl, CH2Ar, aryloxy, hydroxyaryl, heteroaryl, phenyl, vinyl, alkynyl, alkenyl, substituted carbonyl, halo, haloalkyl, nitrile, oxo, substituted oxo, substituted silyl, thiol, benzhydryl, silyl, substituted carboxyl, aminoalkyl, alkoxycarbonyl, alkylamido, furannylalkyl, alkylthioalkyl, arylhydroxyalkyl, indanyl, indolylalkyl, naphthylalkyl, imidazolylalkyl, pyridiylalkyl, phthalimidyl, maleimidyl, benzothiophenylalkyl, thiophenylalkyl, thioalkyl, thioaryl, thiobenzyl, hydroxy, tosyl, nosyl, a protected amine, carboxyl, carboxyalkyloxy, amino, carboxylic acid, haloalkylamido, aldehyde, alkylamino, amido, trityl, tert-butyloxycarbonyl, carbobenzyloxy, acetyl, dimethoxybenzyl, p-methoxybenzyl, any two vicinal carbons of R1 and R2 together form a fused ring, any two geminal carbons, R1 and R2 are bonded together and form a spiro ring, any of R1-4 is attached to chiral carbon, or is one of:
• where n=1-10 and X is hydrogen, halo, cyano, alkyl, aryl, hydroxyl, nitro, amino, alkylamino, dialkylamino, substituted amine, substituted carbonyl, isocyanate, cyanate ester, protected amine, protected hydroxyl, protected carboxyl, boronic acid, borinic acid, borinate ester, triflate, silyl, substituted silyl, thiocyano, isothiocyano, alkoxy, aryloxy, carboxyl, carboxylic acid, carboxyalkyl, carboxyalkyloxy, ester, amido, aldehydo, alkylamido, or haloalkylamido, and/or R3 or R4 can also be selected from:
• where n=1-3 and Ar is an aromatic ring bonded to one of the n carbons;
• R5 is as defined for R1-R4;
• R′ independently is OH, NH2, NR″2, or OR″, wherein R″ independently is alkyl, tert-butyl, allyl, benzyl, CH2Ar, silyl, trityl, an amine protecting group, a carboxyl protecting group, or a hydroxyl protecting group;
• and wherein Ar in CH2Ar represents an aromatic rind;
• and
• stereoselectively or regioselectively reacting the aziridinium ion in situ with a nucleophile in a nucleophilic ring opening reaction to obtain a compound, wherein the compound comprises one of:
• where:
• n=1, 2, or 3;
• Y=O, NH, or S;
• each of each of R1-5 and X are as defined above, and R6 is as defined for R1-5.