Synthesis and Spectral Properties of Amphiphilic Lipids with Linear Conjugated Polyene and Phenylpolyene Fluorescent Groups

Abstract

Lipophilic fluorescent groups with a chain-like linear conformation emitting in the visible range and with high photostability are presently unavailable. These structures would be of great interest as labels for long-chain fatty acids and phospholipids lacking intrinsic fluorescent groups. With this aim in mind, we report the synthesis and the spectroscopic characterization of a series of emitting amphiphilic lipids that may approach that ideal fluorescent tag. Each lipid was constructed by attaching a linear, all-(E) conjugated pentaene, tetraenyne, ω-phenyltetraene, or ω-phenyltrienyne chromophore to a hydrophilic head-group through a polymethylene chain spacer. The key steps of the synthesis were the Pd 0 -mediated cross-coupling reaction between bromopolyenes and terminal acetylenic compounds, yielding tetraenynes or ω-phenyltrienynes, and the subsequent triple-bond partial reduction, producing the corresponding pentaenes or ω-

Synthesis and Biological Evaluation of Fluorescent Leishmanicidal Analogues of Hexadecylphosphocholine (Miltefosine) as Probes of Antiparasite Mechanisms

“…39 Alcohols 6 and 7 were obtained by cross-coupling between bromopolyene 1 and alkyne 5, following reported conditions. 52 all-(E)-13-Phenyltrideca-6,8,10,12-tetraenylphosphocholine (PTE-MT). Trimethylamine (ca.…”

“…39 Briefly (Scheme 1), a Sonogashira- 5), following reported conditions. 52 Pure isomer all-(E)-6 was easily separated from the (8E)/(8Z) mixture by selective precipitation with n-pentane from concentrated CH 2 Cl 2 solutions. Subsequent partial reduction of 6 (pure all-(E) isomer or (8E)/(8Z) mixtures) with activated zinc, and isomerization with iodine of the resulting phenyltetraene, yielded the all-(E) alcohol 7.…”

“…Miltefosine analogues all -( E )-13-phenyltrideca-6,8,10,12-tetraenylphosphocholine (PTE-MT) and all -( E )-13-phenyltrideca-8,10,12-trien-6-ynylphosphocholine (PTRI-MT) were obtained in a similar way, from the corresponding all -( E ) alcohols 7 and 6 . Phenyltrienyne alcohol 6 was synthesized as (8 E ,10 E ,12 E )/(8 Z ,10 E ,12 E ) 3:7 mixture by a similar cross-coupling reaction between bromotriene 1 and hept-6-yn-1-ol ( 5 ), following reported conditions . Pure isomer all -( E )- 6 was easily separated from the (8 E )/(8 Z ) mixture by selective precipitation with n -pentane from concentrated CH 2 Cl 2 solutions.…”

Fluorescent Analogs of Biomolecular Building Blocks: Design, Properties, and Applications

“…A more classical approach involves consecutive Wittig and Wadsworth-Horner-Emmons reactions 219,220. Regardless of the synthetic approach, the final polyene must be isomerized to the all-( E ) isomer, typically by the use of iodine 217,224…”

Miltefosine and BODIPY-labeled alkylphosphocholine with leishmanicidal activity: Aggregation properties and interaction with model membranes

“…In the case of lipid compounds, the design of true fluorescent analogues entails preserving as much as possible the amphiphilic properties of the original structure (25,26). Accordingly, miltefosine fluorescent analogues designed for the study of antiparasitic effects were prepared by attaching a non-polar UV-absorbing phenylpolyene fluorescent group to MT alkyl chain, remaining intact the phosphocholine head group which is essential for the in vivo leishmanicidal effect (17,27). These emitting analogues of MT show the same cytotoxicity as the parent drug against amastigote cultures of L. pifanoi, and a lower but still potent activity against promastigote cultures of L. donovani (17).…”