2,3-Diaminopropanols Obtained from D-Serine As Intermediates in the Synthesis of Protected 2,3-l-Diaminopropanoic Acid (l-Dap) Methyl Esters

Overview

Journal Molecules

Publisher MDPI

Specialty Biology

Date 2020 Mar 19

PMID 32183079

Citations 1

Authors

Andrea Temperini

Donatella Aiello

Fabio Mazzotti

Constantinos M Athanassopoulos

Pierantonio De Luca

Carlo Siciliano

Affiliations

Soon will be listed here.

Abstract

A synthetic strategy for the preparation of two orthogonally protected methyl esters of the non-proteinogenic amino acid 2,3-l-diaminopropanoic acid (l-Dap) was developed. In these structures, the base-labile protecting group 9-fluorenylmethyloxycarbonyl (Fmoc) was paired to the -toluensulfonyl (tosyl, Ts) or acid-labile -butyloxycarbonyl (Boc) moieties. The synthetic approach to protected l-Dap methyl esters uses appropriately masked 2,3-diaminopropanols, which are obtained via reductive amination of an aldehyde prepared from the commercial amino acid -Fmoc---butyl-d-serine, used as the starting material. Reductive amination is carried out with primary amines and sulfonamides, and the process is assisted by the Lewis acid Ti(OPr). The required carboxyl group is installed by oxidizing the alcoholic function of 2,3-diaminopropanols bearing the tosyl or benzyl protecting group on the 3-NH site. The procedure can easily be applied using the crude product obtained after each step, minimizing the need for chromatographic purifications. Chirality of the carbon atom of the starting d-serine template is preserved throughout all synthetic steps.

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References

Antoniou A, Pepe D, Aiello D, Siciliano C, Athanassopoulos C . Chemoselective Protection of Glutathione in the Preparation of Bioconjugates: The Case of Trypanothione Disulfide. J Org Chem. 2016; 81(10):4353-8. DOI: 10.1021/acs.joc.6b00300. View

Xu Z, Wang M, Xiao S, Liu C, Yang M . Synthesis, biological evaluation and DNA binding properties of novel bleomycin analogues. Bioorg Med Chem Lett. 2003; 13(15):2595-9. DOI: 10.1016/s0960-894x(03)00435-9. View

Audic N, Potier G, Sasaki N . New 2,3-diaminopropionic acid inhibitors of AGE and ALE formation. Org Biomol Chem. 2012; 11(5):773-80. DOI: 10.1039/c2ob27084f. View

Roviello G, Musumeci D, Bucci E, Pedone C . Synthesis of a diaminopropanoic acid-based nucleoamino acid and assembly of cationic nucleopeptides for biomedical applications. Amino Acids. 2012; 43(6):2537-43. DOI: 10.1007/s00726-012-1335-6. View

Di Donna L, Mazzotti F, Napoli A, Salerno R, Sajjad A, Sindona G . Secondary metabolism of olive secoiridoids. New microcomponents detected in drupes by electrospray ionization and high-resolution tandem mass spectrometry. Rapid Commun Mass Spectrom. 2007; 21(3):273-8. DOI: 10.1002/rcm.2830. View

Sugiyama M, Kumagai T . Molecular and structural biology of bleomycin and its resistance determinants. J Biosci Bioeng. 2005; 93(2):105-16. DOI: 10.1263/jbb.93.105. View

Siciliano C, Barattucci A, Bonaccorsi P, Di Gioia M, Leggio A, Minuti L . Synthesis of D-erythro-sphinganine through serine-derived α-amino epoxides. J Org Chem. 2014; 79(11):5320-6. DOI: 10.1021/jo500493c. View

Belsito E, Di Gioia M, Greco A, Leggio A, Liguori A, Perri F . N-methyl-N-nosyl-beta(3)-amino acids. J Org Chem. 2007; 72(13):4798-802. DOI: 10.1021/jo070438i. View

Noden M, Moreira R, Huang E, Yousef A, Palmer M, Taylor S . Total Synthesis of Paenibacterin and Its Analogues. J Org Chem. 2019; 84(9):5339-5347. DOI: 10.1021/acs.joc.9b00364. View

10.

Di Gioia M, Leggio A, Liguori A, Perri F, Siciliano C, Viscomi M . A preparation of N-Fmoc-N-methyl-alpha-amino acids and N-nosyl-N-methyl-alpha-amino acids. Amino Acids. 2008; 38(1):133-43. DOI: 10.1007/s00726-008-0221-8. View

11.

Quan K, Li G, Tao L, Xie Q, Yuan Q, Wang X . Diaminopropionic Acid Reinforced Graphene Sponge and Its Use for Hemostasis. ACS Appl Mater Interfaces. 2016; 8(12):7666-73. DOI: 10.1021/acsami.5b12715. View

12.

Xue C, Roderick J, Jackson S, Rafalski M, Rockwell A, Mousa S . Design, synthesis, and in vitro activities of benzamide-core glycoprotein IIb/IIIa antagonists: 2,3-diaminopropionic acid derivatives as surrogates of aspartic acid. Bioorg Med Chem. 1997; 5(4):693-705. DOI: 10.1016/s0968-0896(97)00013-8. View

13.

Featherston A, Shugrue C, Mercado B, Miller S . Phosphothreonine (pThr)-Based Multifunctional Peptide Catalysis for Asymmetric Baeyer-Villiger Oxidations of Cyclobutanones. ACS Catal. 2019; 9(1):242-252. PMC: 6467539. DOI: 10.1021/acscatal.8b04132. View

14.

Deetz M, Forbes C, Jonas M, Malerich J, Smith B, Wiest O . Unusually low barrier to carbamate C-N rotation. J Org Chem. 2002; 67(11):3949-52. DOI: 10.1021/jo025554u. View

15.

Aiello D, Giambona A, Leto F, Passarello C, Damiani G, Maggio A . Human coelomic fluid investigation: A MS-based analytical approach to prenatal screening. Sci Rep. 2018; 8(1):10973. PMC: 6054674. DOI: 10.1038/s41598-018-29384-9. View

16.

Huang L, Teumelsan N, Huang X . A facile method for oxidation of primary alcohols to carboxylic acids and its application in glycosaminoglycan syntheses. Chemistry. 2006; 12(20):5246-52. PMC: 1986577. DOI: 10.1002/chem.200600290. View

17.

Siciliano C, De Marco R, Guidi L, Spinella M, Liguori A . A one-pot procedure for the preparation of N-9-fluorenylmethyloxycarbonyl-α-amino diazoketones from α-amino acids. J Org Chem. 2012; 77(23):10575-82. DOI: 10.1021/jo301657e. View

18.

Kobylarz M, Grigg J, Takayama S, Rai D, Heinrichs D, Murphy M . Synthesis of L-2,3-diaminopropionic acid, a siderophore and antibiotic precursor. Chem Biol. 2014; 21(3):379-88. DOI: 10.1016/j.chembiol.2013.12.011. View

19.

Di Donna L, Benabdelkamel H, Taverna D, Indelicato S, Aiello D, Napoli A . Determination of ketosteroid hormones in meat by liquid chromatography tandem mass spectrometry and derivatization chemistry. Anal Bioanal Chem. 2015; 407(19):5835-42. DOI: 10.1007/s00216-015-8772-5. View

20.

De Marco R, Di Gioia M, Leggio A, Liguori A, Perri F, Siciliano C . A new non-natural arginine-like amino acid derivative with a sulfamoyl group in the side-chain. Amino Acids. 2009; 38(3):691-700. DOI: 10.1007/s00726-009-0267-2. View