1 Technical Study On Synthesis Of Paricalcitol 2 The Research Of Olefin Dihydroxylation Reaction Under Non Water Condition

The first part of this paper mainly focused on the design and total synthesis of Paricalcitol.Paricalcitol(Chemical Name:1?,25-dihydroxyvitamin D2),which trade name is Zyperxa,was firstly approved in USA in 1998 for treatment of secondary hyperparathyroidism(SHPT)patients.It can effectively lower the thyroid hormone(PTH)levels,while have little impact on the concentration of calcium and phosphate ions in the blood.Based on the investigation of published papers on the synthesis of Paricalcitol,this paper proposed a green,efficient and economic new synthetic route for Paricalcitol.This route adopted convergent synthesis methodology,in which ring A was synthesized starting from quinic acid in 10 steps,with a total yield of 15%.Ring C/D was synthesized from Vitamin D2 in 8 steps with a total yield of 8%.Thetwo ring were subjected to a Witting reaction,followed by deprotection to furnished the synthesis of Paricalcitolwith a total yield of about 5% calculated from Vitamin D2.This route was superior to the published literature in both cost and isolated yield.The second part of this paper mainly studied the olefin dihydroxylation reaction mediated by quaternary ammonium.Vicinal diols is very important intermediates in organic synthesis,especially in the asymmetric synthesis of natural products and drugs,thusmethodology for preparation vicinal diols raised the value of both research and application.This paper proposed a new type of benzyl triethyl ammonium chloride(TEBAC)/potassium permanganate/acetone system for the dihydroxylation of olefins,satisfictory results were achieved.The third part of this paper mainly studied the synthesis of a new type of chiral diamine ligand and its application in asymmetric lithiation.Starting from chiral cyclohexanediamine,after acylation,reduction and methylation,the target chiral diamine ligand was synthesis in high yield.2-Bromo-N,N-bis(phenylmethyl)-benzamidewas choosed as substrate for the subsequent asymmetric lithation,followed by quench with benzoaldehyde derivatives,but the e.e valuewas very low.The scope research of this asymmetric lithiation on substrate and electrophilic reagent was under process.