(3S,4S)-3-Aminotetrahydro-2H-pyran-4-ol
[CAS# 1240390-32-2]

Identification

• Classification: Pharmaceutical intermediate >> Heterocyclic compound intermediate >> Pyran compound
• Name: (3S,4S)-3-Aminotetrahydro-2H-pyran-4-ol
• Synonyms: 2-Amino-1,5-anhydro-2,4-dideoxy-L-threo-pentitol
• Molecular Formula: C₅H₁₁NO₂
• Molecular Weight: 117.15
• CAS Registry Number: 1240390-32-2
• SMILES: C1COC[C@@H]([C@H]1O)N

Properties

• Density: 1.1±0.1 g/cm³ Calc.^*
• Boiling point: 246.8±40.0 ºC 760 mmHg (Calc.)^*
• Flash point: 103.0±27.3 ºC (Calc.)^*
• Solubility: water Very soluble (1000 g/L) (25 ºC), Calc.
• Index of refraction: 1.496 (Calc.)^*

^* Calculated using Advanced Chemistry Development (ACD/Labs) Software.

Safety Data

• Hazard Symbols: GHS07 Warning
• Hazard Statements: H302-H315-H319-H335
• Precautionary Statements: P261-P305+P351+P338

Discovory and Applicatios

(3S,4S)-3-Aminotetrahydro-2H-pyran-4-ol is a chiral amino alcohol scaffold that has emerged as a valuable building block in medicinal chemistry and synthetic methodology development. Structurally, it is a substituted tetrahydropyran bearing a primary amine at the 3-position and a secondary alcohol at the 4-position; the (3S,4S) stereochemistry denotes a trans relationship between these functional groups. The combination of polarity, hydrogen-bonding capacity and defined three-dimensionality makes this motif attractive for incorporation into small-molecule kinase inhibitors and other bioactive compounds where control of solubility, conformation and target engagement is important.

The chemical has been used primarily as a synthetic intermediate and fragment in lead optimization campaigns rather than being an end-use active pharmaceutical ingredient by itself. Examples in the literature show the 3-aminotetrahydropyran subunit incorporated into diaminopyrimidine and triazine scaffolds that target spleen tyrosine kinase (SYK). In medicinal chemistry programmes directed at SYK, corresponding aminotetrahydropyran-containing intermediates were advanced through structure-based design and whole-blood activity optimisation to give potent, selective inhibitors with oral efficacy in animal models. Those studies demonstrate how the 3-aminotetrahydropyran element can contribute to favourable pharmacokinetic and pharmacodynamic properties when embedded in larger heterocyclic frameworks.

Beyond its role in drug discovery projects, the aminotetrahydropyran motif has attracted interest from synthetic chemists seeking efficient, stereoselective methods to access substituted tetrahydropyrans. Recent methodological advances enable direct C–H functionalization and sequential transformations on simple aminotetrahydropyran cores to install diverse substituents with control over stereochemistry. These routes provide streamlined access to libraries of C3- and C5-functionalised amino-THP derivatives, facilitating rapid exploration of structure–activity relationships in medicinal chemistry programs. The development of catalytic, stereospecific protocols has also reduced the reliance on lengthy multi-step classical sequences, improving atom economy and accelerating compound synthesis at discovery scale.

In practical terms, researchers obtain enantiomerically enriched (3S,4S) or related stereoisomers either by asymmetric synthesis or by resolution techniques, and the protected aminotetrahydropyran derivatives are routinely elaborated through amide formation, heteroaryl coupling, or reductive amination to create more complex drug-like molecules. The amino and hydroxy functionalities offer orthogonal handles for diversification: the amine can be converted to amides, sulfonamides or heterocycles, while the alcohol can be esterified or used in intramolecular cyclizations to form bicyclic systems. These transformations underpin the motif’s utility as a modular fragment in lead optimisation.

Applications reported in the literature are mostly in early-stage drug discovery and preclinical pharmacology, where aminotetrahydropyran-containing analogues have been profiled for target potency, selectivity and in vivo activity. In the specific case of SYK inhibitors, compounds incorporating the aminotetrahydropyran fragment have shown inhibition of immunoglobulin-mediated responses in rodent models, supporting the scaffold’s compatibility with the physicochemical and biological requirements of oral small-molecule therapeutics directed at immune-related targets.

Overall, (3S,4S)-3-aminotetrahydro-2H-pyran-4-ol is best described as a privileged synthetic building block rather than a standalone therapeutic agent. Its adoption in several medicinal chemistry programs and the recent methodological literature that streamlines access to highly substituted derivatives together validate its standing as a practical and versatile fragment for medicinal chemists designing polar, three-dimensional small molecules.

References

Liddle J, Atkinson FL, Barker MD, Carter PS, Curtis NR, Davis RP, Douault C, Dickson MC, Elwes D, Garton NS, Gray M, Hayhow TG, Hobbs CI, Jones E, Leach S, Leavens K, Lewis HD, McCleary S, Neu M, Patel VK, Preston AG, Ramirez-Molina C, Shipley TJ, Skone PA, Smithers N, Somers DO, Walker AL, Watson RJ, Weingarten GG (2011) Discovery of GSK143, a highly potent, selective and orally efficacious spleen tyrosine kinase inhibitor. Bioorg Med Chem Lett 21 6188–6194 DOI: 10.1016/j.bmcl.2011.07.082

Hayashi H, Kaneko R, Demizu S, Akasaka D, Tayama M, Harada T, Irie H, Ogino Y, Fujino N, Sasaki E (2018) TAS05567, a novel potent and selective spleen tyrosine kinase inhibitor, abrogates immunoglobulin-mediated autoimmune and allergic reactions in rodent models. J Pharmacol Exp Ther 366 84–95 DOI: 10.1124/jpet.118.248153

Kang G, Xiao LJ, Hesp KD, Huh CW, Lian Y, Richardson P, Schmitt DC, Hong K, Yu J-Q (2024) Synthesis of highly substituted aminotetrahydropyrans enabled by stereospecific multivector C–H functionalization. Org Lett 26 2729–2732 DOI: 10.1021/acs.orglett.3c01439