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ChiroSolve Inc. 2065 Martin Ave, Suite 107, Santa Clara, CA 95050, USA ; Telephone: +1(408) 834-8597; Fax: +1(408) 351-7900; http://www.chirosolve.com

Vol 2, Issue 1   

CHIROSOLVE MONTHLY NEWSLETTER  

News You Can Use  

March 2011 Newsletter   

FEATURED CHART  

Solubility phase diagram

DDS and UDS in the optimal resolution system (0.35 mol equiv of D-DATA, THF/H2O, 80/20). Maximum resolution efficiency ) 2 × [(OC - AB)/(AC - AB) ) 2 × [(36 - 14)/(86 - 14)] ) 0.61

Featured chart 2

Source: http://pubs.acs.org/doi/pdf/10.1021/op1002402

 

FEATURED MOLECULE

 

featured molecule 2-2011 6
Source: http://www.epa.gov/athens/research/process/chiralchemistry.html

 

FEATURED ARTICLES

 

Rational Screening Approach for Classical Chiral Resolution under Thermodynamic Equilibrium: A Case Study of Diphenyl-Substituted N-Methyl-Piperazine  (see more >>>)


Chiral Chemistry: the ultimate in pollutant speciation (see more >>>)


Molecular Models of Chiral Molecules:
Metolachlor, Chiralane, Nanotubes, Helicenes, Hexol, and BINAP
(see more >>>)


Chirally Pure S-Metoprolol - Place in Therapy (see more >>>)

 

detectiveDid you know this?

 
Chiral molecules  commonly comprise a carbon atom attached to four different substituents. The substituents can be either atoms or groups of atoms, but each must differ from the other three for the carbon atom to be a chiral center (stereocenter)

A molecule with a single tetrahedral carbon bonded to four different groups will always be chiral; while a molecule with more than one tetrahedral carbon bonded to four different groups is not always chiral

Many chiral molecules have more than one stereocenter. Also, the stereo center of a chiral molecule need not be a carbon atom. Furthermore, some chiral molecules lack a stereocenter that has at least four substituents
 
QUICK LINKS  
 

ChiroSolve, Inc.

2065 Martin Ave, Suite 107

Santa Clara, Ca 95050, USA

 Phone: +1 (408) 834-8597;

Fax: +1 (408) 351-7900

E-Mail: info@chirosolve.com

 

Dear Chiral Chemistry Colleague,

Welcome back to ChiroSolve Monthly Newsletter, designed to bring insightful and timely information on trends and technology to innovators in Organic Chemistry.

In this issue, we are very excited to announce the launch of TWO NEW PRODUCTS that streamline the whole process of method development to prepare pure enantiomer through chiral resolution; and further method optimization that defines the shortest path to obtain enantiomer with target purity and that maximizes the yield; all in matter of days.

ChiroSolve Launches New Chiral Separation Solutions

ChiroSolve has been very successful in producing line of chiral kits that streamline the chiral separation method development. It continues to enhance enantiomeric separation with the introduction of TWO NEW package solutions tailor made for scientists at different stages of their research: ENANTIOPREP and SCALEPREP. Together, these solutions offer seamless transition from the development of pure enantiomers for testing in discovery to fully optimized method development suitable for kilo quantity manufacturing.
 
EnantioPrep is used by scientists to produce pure enantiomer for lead optimization and preclinical assessments.  It includes the components to be used in a simple 3-step process:

  • Screen to identify best separation candidates
  • Recover to recover the racemate used for further purification
  • Purify to perform series of re-crystallization steps until target enantiomeric purity is achieved

It establishes a complete step by step procedure for developing enantiopure compound; and delivers up to 5 gm of pure enantiomer

ScalePrep is targeted at those scientists looking to establish an optimized production-route that can be scaled up to provide kilo quantities of pure enantiomer. It includes the components that allow:

  • Screen to identify best separation candidates
  • Purify to find shortest path to prepare pure enantiomer
  • Optimize to improve the defined method. It explores what ratio between racemate to reagent offers fastest route; and what concentration of solvent offers highest yield
ENANTIOPREP (ideal for Medchem projects) SCALEPREP (ideal for process development projects)
Delivers enantiopure compound Delivers an optimal scale-up process
Results within 7 to 10 days Results in two weeks
Three step process:
  1. Screening: Racemate is screened against 384 combinations and the best is chosen
  2. Recovery: Racemate is recovered for further purification (up to  90% recovery)
  3. Purification: Selected separatin condition is used to purify recovered racemate using series of re-crystallization steps
Three step process:
  1. Screening: Racemate screened against 384 combinations and the best 3 conditions are selected
  2. Purification: Using the best 3 separation conditions, racemate is purified to identify which condition offers target purity with minimum number of steps
  3. Optimization: Using various ratios between racemate and reagents (in form of kit); and using various concentrations of solvents, identify the optimized method
Up to  5g of pure enantiomer and detailed step by step process is defined Up to 20 gm of pure enantiomer is obtained; Detailed optimized separation process that can be scaled up to kilo quantities is defined

ChiroSolve also offers a set of services to complement these products enabling customers to outsource their enantiomer separation and method development optimization projects.Please contact us to learn more.

 

Rational Screening Approach for Classical Chiral Resolution under Thermodynamic Equilibrium: A Case Study of Diphenyl-Substituted N-Methyl-Piperazine

By: Helming Tan, Sheng Cui, Kyung Gahm, Van Luu, and Shawn D. Walker

Org. Process Res. Dev., 2011, 15 (1), pp 53–63

DOI: 10.1021/op1002402

Publication Date (Web): November 17, 2010

Copyright © 2010 American Chemical Society

Separation of racemic mixtures by the formation and crystallization of diastereomeric salts (classical resolution) is an important process in the pharmaceutical industry. We have developed and implemented a high-throughput screening workflow to effectively guide the development and optimization of a thermodynamically favored resolution process. A case study is presented for optical resolution of a diphenyl-substituted N-methyl-piperazine derivative, a racemic compound with a eutectic point of 60% ee. Through a rational screening approach, the effect of equilibrium solubility on resolution efficiency was systematically evaluated with regards to resolving agent, solvent composition, resolving agent stoichiometry, and racemate concentration. An isothermal solubility phase diagram was obtained, and solid-state characterization was performed on the diastereomeric salts to understand their phase behaviors under the optimal resolution conditions. The highest resolution efficiency was achieved when the diastereomeric hemisalt tetrahydrate was formed with 0.35 mol equiv of di-p-anisoyl-d-tartaric acid in THF/H2O (80/20, v/v), while a solid solution of desired and undesired diastereomeric salts crystallized with 70% de. After salt break, the desired enantiomer was upgraded to 98% ee by recrystallization twice in n-heptane. These screening results led to a successful resolution of 30 g racemate with a yield of 37%. This case study demonstrated that the rational screening approach is effective in guiding scale-up for classical chiral resolution under thermodynamic equilibrium. (see more >>>)

 
    Copyright 2010 Chirosolve, Inc. All rights reserved.                                                            Vol2, Issue1 March 2011 Newsletter




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