Chiral and specialty building blocks: Production route
Four ways to make a molecule with only one hand
What this tab covers How it is made: the main production routes or, for product families, the main product types and technologies, compared on share of supply, inputs per tonne, plant scale, yield, co-products and unit cost.There are four ways to get a single-handed molecule. Start from a natural chiral molecule (chiral pool). Make the racemic mixture and separate it, by crystallising salts with a chiral acid or base or by chiral chromatography. Make only one hand directly with a chiral metal catalyst. Or use an enzyme, which is naturally selective. Resolution is cheapest to develop but wastes half the material unless the unwanted half is racemised and recycled; catalysis and enzymes cost more to develop but less to run at scale.
Routes compared
| Route | Share of supply | Inputs per tonne | Typical scale | Yield | Co-products | Unit cost |
|---|---|---|---|---|---|---|
| Classical resolution (diastereomeric salt crystallisation) | 45.2% of chiral chemicals market by technology (IMARC 2025) | at least 2 t racemate per t product without recycling; resolving agent largely recovered (indicative) | tonnes to thousands of tonnes a year | maximum 50% per pass unless the other enantiomer is racemised and recycled | unwanted enantiomer, solvents and salts | not published |
| Asymmetric catalysis (hydrogenation, epoxidation) | part of 'asymmetric preparation' (IMARC; share not published) | catalyst loadings often 0.001-0.1 mol% (indicative) | up to about 10 kt/yr for S-metolachlor by iridium-Josiphos hydrogenation, the largest industrial example (indicative) | often over 95% with over 95% ee (indicative) | little; spent precious-metal catalyst recovered | precious metal and ligand costs offset by high yield (indicative) |
| Biocatalysis (engineered enzymes) | part of 'biological separation' and asymmetric methods (IMARC; share not published); growing | enzyme typically a few percent by weight of substrate (indicative) | kg to several kt/yr; BASF ChiPros chiral amines via lipase resolution (indicative) | high ee, often over 99% (indicative) | aqueous waste, spent enzyme | enzyme development costs up front; low running cost (indicative) |
| Chiral pool synthesis | not published | varies | large for amino acid- and sugar-derived blocks | depends on steps | protecting-group waste | follows fermentation and crop prices |
| Chiral chromatography (simulated moving bed, SMB) | small (indicative) | large solvent volumes, mostly recycled | up to hundreds of t/yr (indicative) | over 95% recovery of the desired enantiomer (indicative) | unwanted enantiomer, solvent | high; used when other routes fail (indicative) |
How each route works
Classical resolution (diastereomeric salt crystallisation)A racemic acid or amine is reacted with a chiral resolving agent, such as tartaric acid, mandelic acid or a chiral amine. The two salts have different solubilities and one crystallises; the free compound is then released and the agent recovered.
Simple, robust and well understood by Indian and Chinese makers; wasteful without recycling.
IMARC (2026); indicative Asymmetric catalysis (hydrogenation, epoxidation)A metal catalyst (rhodium, ruthenium or iridium) with a chiral ligand such as BINAP or Josiphos adds hydrogen or oxygen to one face of a molecule. Knowles, Noyori and Sharpless shared the 2001 Nobel Prize for this.
Efficient and scalable; needs high-pressure hydrogen and removal of metal residues to ppm levels (ICH Q3D).
Nobel Prize 2001; indicative Biocatalysis (engineered enzymes)Ketoreductases, transaminases, lipases and nitrilases convert a substrate to one enantiomer in water or mild solvents. Directed evolution tailors enzymes to industrial substrates.
Mild, selective, often greener; each enzyme must be engineered for each substrate.
Savile et al., Science 2010 (indicative); IMARC company list (Codexis, BASF) Chiral pool synthesisNatural chiral molecules such as amino acids, sugars, tartaric acid, lactic acid and terpenes (e.g. limonene) are converted into building blocks while keeping their handedness.
Cheap where nature provides the right skeleton; limited choice of structures.
indicative Chiral chromatography (simulated moving bed, SMB)The racemate is pumped through columns packed with a chiral stationary phase; one enantiomer elutes first. SMB runs continuously at production scale.
Fast to develop for early clinical supply; expensive at scale.
indicative; Daicel Chiral Technologies (IMARC company list) Unit economics are indicative ranges from the sources named; costs move with feedstock and energy prices, plant size and region.