Prenalterol

Prenalterol

Systematic (IUPAC) name
4-{[(2S)-2-hydroxy-3-(isopropylamino)propyl]oxy}phenol
Clinical data
Routes of administration	Oral, IV
Legal status
Legal status	℞ (Prescription only)
Identifiers
CAS Number	57526-81-5
ATC code	C01CA13 (WHO)
PubChem	CID 42396
IUPHAR/BPS	537
ChemSpider	38665
UNII	M4G34404CX
ChEMBL	CHEMBL1160714
Chemical data
Formula	C12H19NO3
Molar mass	225.284 g/mol
SMILES O(c1ccc(O)cc1)C[C@@H](O)CNC(C)C
InChI InChI=1S/C12H19NO3/c1-9(2)13-7-11(15)8-16-12-5-3-10(14)4-6-12/h3-6,9,11,13-15H,7-8H2,1-2H3/t11-/m0/s1 Key:ADUKCCWBEDSMEB-NSHDSACASA-N
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Prenalterol is a cardiac stimulant which acts as a β₁ adrenoreceptor agonist.^[1]

Synthesis

Stereospecific

Prenalterol interestingly exhibits adrenergic agonist acitivity in spite of an interposed oxymethylene group. The stereospecific synthesis devised for this molecule relies on the fact that the side chain is very similar in oxidation state to that of a sugar.

Prenalterol synthesis:^[2][3]

Condensation of the monobenzyl ether of phenol (1) with the epoxide derived from α-D-glucofuranose^[4] affords the glycosylated derivative (3). Hydrolytic removal of the acetonide protecting groups (cf. eg)^[5] followed by cleavage of the sugar with periodate gives aldehyde (4). This is reduced to the glycol by means of NaBH₄ and the terminal alcohol is converted to the mesylate (5). Displacement of the leaving group with isopropylamine followed by hydrogenolytic removal of the O-benzyl ether affords the β₁-adrenergic selective adrenergic agonist prenalterol (6).

Racemic

Prepns of the racemic mixture: NL 6409883  corresp to H. Köppe et al., U.S. Patent 3,637,852 (1965, 1972 both to Boehringer Ingelheim); NL 301580  corresp to A. F. Crowther, L. H. Smith, U.S. Patent 3,501,769 (1965, 1970 both to ICI);^[6]

Further Reading

• Acta Medica Scandinavica 211. 1982. doi:10.1111/joim.1982.211.issue-s659. Missing or empty |title= (help)

See also

• Primidolol

References

1. Hadfield SE, Slee SJ, Snow HM (1989). "The cardiovascular pharmacology of xamoterol, cicloprolol, prenalterol and pindolol in the anaesthetised dog". Br J Clin Pharmacol. 28 Suppl 1 (Suppl 1): 78S–81S. doi:10.1111/j.1365-2125.1989.tb03580.x. PMC 1379883. PMID 2572262.
2. K. A. Jaeggi, H. Schroeter, and F. Ostermayer, DE 2503968 ; Chem. Abstr. 84, 5322 (1976).
3. corresp to U.S. Patent 3,978,041 and U.S. Patent 4,049,797 (1975, 1976, 1977, all to Ciba-Geigy).
4. http://www.chemspider.com/Chemical-Structure.9312824.html
5. Liu, Z; Hu, B. H.; Messersmith, P. B. (2010). "Acetonide Protection of Dopamine for the Synthesis of Highly Pure N-docosahexaenoyldopamine". Tetrahedron Letters 51 (18): 2403–2405. doi:10.1016/j.tetlet.2010.02.089. PMC 2882309. PMID 20543896.
6. Crowther, Albert F.; Gilman, D. J.; McLoughlin, B. J.; Smith, Leslie Harold; Turner, R. W.; Wood, T. M. (1969). ".beta.-Adrenergic blocking agents. V. 1-Amino-3-(substituted phenoxy)-2-propanols". Journal of Medicinal Chemistry 12 (4): 638. doi:10.1021/jm00304a018. PMID 5793156.