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Synthesis of 1,3- and 1,2-Diphosphatidylglycerol

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Lipids

Abstract

A novel phosphonium salt methodology was utilized for the first time to synthesize 1,3-, and 1,2-diphosphatidylglycerol. Optically active 1,2-di-O-acyl-sn-glyceryl phosphate was coupled with unprotected glycerol in the presence of pyridiniumbromide perbromide and triethylamine to yield, after final removal of phosphate protecting group, the title compounds. The 1,2-diphosphatidylglycerol (1,2-isomer of cardiolipin) may be a member of a new class of phospholipids for industrial applications similar to other phosphocholines.

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Abbreviations

ATR:

Attenuated total reflectance

CL:

Cardiolipin

DIPEA:

Diisopropylethylamine

ESI:

Electron spray ionization

IR:

Infra red

MS:

Mass spectrometry

NMR:

Nuclear magnetic resonance

PA:

Phosphatidic acid

PBP:

Pyridiniumbromide perbromide

PG:

Phosphatidylglycerol

rt:

Room temperature

TBHP:

tert-Butylhydroperoxide

THF:

Tetrahydrofuran

TLC:

Thin layer chromatography

References

  1. Arrigo PD, Ferra LD, Fantoni GP, Scarcelli D, Servi S, Strini A (1996) Enzyme-mediated synthesis of two diastereoisomeric forms of phosphatidylglycerol and of diphosphatidylglycerol (cardiolipin). J Chem Soc Perkin Trans 1(21):2657–2660

    Article  Google Scholar 

  2. Keana JFW, Shimiju M, Jernstedt KK (1986) A short, flexible route to symmetrically and unsymmetrically substituted diphosphatidylglycerols (cardiolipin). J Org Chem 51:2297–2299

    Article  CAS  Google Scholar 

  3. Mishina IM, Vasilenko AE, Stepanov AE, Shvets VI (1987) Studies on complex lipids. Synthesis of diphosphatidylglycerol (cardiolipin) with unsaturated fatty acids. Bioorg Khim 13:1110–1115

    PubMed  CAS  Google Scholar 

  4. Mishina IM, Vasilenko AE, Stepanov AE, Shvets VI (1984) Study of lipids. Synthesis of phosphatidylglycerol and diphosphatidylglycerol. Zh Org Khim 20:985–988

    Google Scholar 

  5. Mishina IM, Vasilenko AE, Stepanov AE, Shvets VI (1985) Synthesis of diphosphatidylglycerol (cardiolipin) with unsaturated fatty acids. Bioorg Khim 11:992–994

    CAS  Google Scholar 

  6. Ioannou PV, Marecek JF (1986) Studies on the chemical synthesis and stability of cardiolipins and related compounds. Chem Chorn 15:205–220

    CAS  Google Scholar 

  7. Ramirez F, Ioannou PV, Marecek JF, Dodd GH, Golding BT (1977) Synthesis of phospholipids by means of cyclic enediol pyrophosphates. Tetrahedron 33:599–608

    Article  CAS  Google Scholar 

  8. Ramirez F, Ioannou PV, Marecek JF, Golding BT, Dodd GH (1976) Application of cyclic enediol pyrophosphates to the synthesis of phospholipids. Diphosphatidylglycerol (cardiolipin). Synthesis 11:769–770

    Article  Google Scholar 

  9. Inoue K, Nojima S (1968) Immunochemical studies of phosoholipids. II. Synthesis of cardiolipin and its analogues. Chem Pharm Bull 16:76–81

    PubMed  CAS  Google Scholar 

  10. Inoue K, Nojima S (1963) On the cardiolipin analogues. Synthesis of dipalmitoyl-d,l-α-glycerylphosphoryl-propanol sodium salt and bis(dipalmitoyl-d,l-α-glycerylphosphoryl)-1,3-propanediol disodium salt. Chem Pharm Bull 11:1150–1156

    PubMed  CAS  Google Scholar 

  11. Saunders RM, Schwarz HP (1966) Synthesis of phosphatidylglycerol and diphosohatidylglycerol. J Am Chem Soc 88:3844–3847

    Article  PubMed  CAS  Google Scholar 

  12. Duralski AA, Spooner PJR, Rankin SE, Watts A (1998) Synthesis of isotopically labelled cardiolipins. Tetrahedron Lett 39:11607–1610

    Article  Google Scholar 

  13. Krishna UM, Ahmad MU, Ahmad I (2004) Phosphoramidite approach for the synthesis of cardiolipin. Tetrahedron Lett 45:2077–2079

    Article  CAS  Google Scholar 

  14. Lin Z, Ahmad MU, Ali SM, Ahmad I (2004) An efficient and novel method for the synthesis of cardiolipin and its analogs. Lipids 39:285–290

    Article  PubMed  CAS  Google Scholar 

  15. Krishna UM, Ahmad MU, Ali SM, Ahmad I (2004) A short, concise route to diphosphatidylglycerol (cardiolipin) and its variants. Lipids 39:595–600

    Article  PubMed  CAS  Google Scholar 

  16. Browne JE, Driver MJ, Russel JC, Sammes PG (2000) Preparation of phospholipid analogues using the phosphoramidite route. J Chem Soc Perkin Trans 1(5):653–657

    Article  Google Scholar 

  17. Beaucage SL, Iyer RP (1993) The synthesis of specific ribonucleotides and unrealated phosphorylated biomolecules by the phosphoramidite method. Tetrahedron 49:10441–10488

    Article  CAS  Google Scholar 

  18. Watanaba Y, Hirofuji H, Ozaki S (1994) Synthesis of a phosphatidylinositol 3, 4, 5-triphosphate. Tetrahedron Lett 35:123–124

    Article  Google Scholar 

  19. Watanaba Y, Nakamura T, Mitsumoto H (1997) Protection of phosphate with the 9-fluorenylmethyl group. Synthesis of unsaturated-acyl phosphatidylinositol 4, 5-bisphosphate. Tetrahedron Lett 38:7407–7410

    Article  Google Scholar 

Download references

Acknowledgments

We thank the Bioanalytical group of Pharmacokinetics, Safety and Efficacy (PSE) Department at NeoPharm for the Mass spectral analyses.

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Author notes

  1. Moghis U. Ahmad & Shoukath M. Ali

    Present address: Jina Pharmaceuticals, Inc., 28100 N. Ashley Circle, Suite 103, Libertyville, IL, 60048, USA

  2. U. Murali Krishna

    Present address: New River Pharmaceuticals, 1881 Grove Ave., Radford, VA, 24141, USA

Authors and Affiliations

  1. NeoPharm, Inc., 1850 Lakeside Drive, Waukegan, IL, 60085, USA

    Moghis U. Ahmad, U. Murali Krishna, Shoukath M. Ali, Sreeti Choudhury & Imran Ahmad

  2. Jina Pharmaceuticals, Inc., 28100 N. Ashley Circle, Suite 103, Libertyville, IL, 60048, USA

    Imran Ahmad

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  1. Moghis U. Ahmad
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  2. U. Murali Krishna
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  3. Shoukath M. Ali
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  4. Sreeti Choudhury
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  5. Imran Ahmad
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Correspondence to Imran Ahmad.

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Ahmad, M.U., Krishna, U.M., Ali, S.M. et al. Synthesis of 1,3- and 1,2-Diphosphatidylglycerol. Lipids 42, 291–296 (2007). https://doi.org/10.1007/s11745-007-3020-1

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  • DOI: https://doi.org/10.1007/s11745-007-3020-1

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