Structure determinations and synthesis of pharmacologically active phospholipids from kidney and intestine

Abstract

The chemical structures of an acidic phospholipid originally isolated from equine intestine by Vogt and of a phospholipid isolated from rabbit kidney medulla by Walaszek are shown by total synthesis to be similar mixtures of 2‐alkyl (and alkenyl)‐4‐hydroxymethyl‐1,3‐dioxolane‐dihydrogen phosphate esters. In these materials, the alkyl residues derive primarily from oleyl, palmityl and linoleyl aldehydes. The smooth muscle contracting activity observed in the natural substances is shown to reside exclusively in the oleyl aldehyde derivative.

Acetal phosphatidic acids: novel platelet aggregating agents

“…PGAP comprised 17% of the acetal phosphatidic acid complement of 'Darmstoff' isolated from horse intestine and 32% of that prepared from rabbit kidney (Wiley et al, 1970). The platelet aggregating potencies of PGAP, LGAP and OGAP make it tempting to speculate that the compounds may be of physiological or pathological importance in vivo.…”

Cyclic Glycerol Acetals from the Abdominal Hair Pencil Secretion of the Male African Sugarcane Borer Eldana saccharina (Lepidoptera: Pyralidae)

“…O n the basis o f ch ro m ato g rap h ic evidence it was suggested th at the active principle was a long-chain cyclic glycerol acetal p h o sp h ate 5 [12,13]. D a rm sto ff w as subse q uently found in o th er m am m alian and am phibian organs [14] an d it was found to consist o f a m ixture o f 2-alkyl-and 2-alkenyl-4-hydroxym ethyl-l,3-dioxolanedihydrogen p h o sp h ate esters, the 2-alkyl and -alkenyl residues being derived prim arily from hexadecanal and Z -9-octadecenal [15]. The sm ooth m uscle co n tractin g activity was show n to reside exclusively in the Z -9-octadecenal deriva-…”

“…N o long-chain dioxane derivatives were found in extracted m aterial show ing D arm sto ff activity [15].…”

Identification of Darmstoff analogs as selective agonists and antagonists of lysophosphatidic acid receptors

“…Interestingly, all the intestinal smooth muscle contracting activity possessed by Darmstoff resides in the oleyl acetal 1b. 18,19 These compounds were also shown to display hypotensive and cardiodepressant properties 20 and stimulate platelet aggregation. Vogt was also the first to describe an LPA-induced physiological response.…”

“…Previously reported methods 19,22 for the synthesis of this compound class have limitations and are particularly unsuitable for the preparation of Darmstoff analogs containing thiophosphate head groups. To facilitate the synthesis of various Darmstoff analogs in an effort to develop a structure-activity relationship, we developed a general method for the preparation of these compounds utilizing phosphoramidite chemistry.…”