Synthesis of Nontoxic Fluorous Sphingolipids as Molecular Probes of Exogenous Metabolic Studies for Rapid Enrichment by Fluorous Solid Phase Extraction

Abstract

Fluorous solid‐phase extraction (FSPE) is a useful technique for efficient selective enrichment of fluorous compounds from nonfluorous molecules. Sphingolipids and their metabolites, which are ubiquitous building blocks of eukaryotic and prokaryotic cell membranes, play crucial roles, for example, as signaling molecules. However, details of the functions and metabolic mechanisms of exogenous sphingolipids have remained unknown compared with those of their endogenous analogs. To better understand these unknown roles, chemical probes with appropriate biological and physicochemical properties are needed. In this study, we designed and synthesized new fluorous sphingolipids to reveal these roles. Furthermore, we confirmed that they could be efficiently and rapidly separated from normal sphingolipids by FSPE, and that they hardly showed any cytotoxic activity, similarly to normal sphingolipids at the same dose. We also showed that these fluorinated ceramides could act as metabolic substrates for sphingomyelin synthase 2 (SMS2). This demonstrates their potential for further biological studies.

Evaluation of chiral N,N‐dimethyl‐sphingosine for the interaction between nerve growth factor and tropomyosin receptor kinase A

“…First, we started to prepare both d ‐ erythro ‐sphingosine and l ‐ erythro ‐sphingosine ( 6 ) from l ‐ or d ‐serine according to our previous report with slight modification 12 . In deprotection of the oxazolidine ( 5 ), by reducing the reaction temperature and time compared with the previous condition, we could prevent the side reactions: isomerization and rearrangement of the allylic 3‐alcohol.…”

“…First, we started to prepare both D-erythro-sphingosine and L-erythro-sphingosine (6) from L-or D-serine according to our previous report with slight modification. 12 In deprotection of the oxazolidine (5), by reducing the reaction temperature and time compared with the previous condition, we could prevent the side reactions: isomerization and rearrangement of the allylic 3-alcohol. Subsequently, the dimethylation of amino group was subjected to reductive alkylation with aqueous formaldehyde in the presence of sodium cyanoborohydride under weak acidic condition (Scheme 1).…”

Stereochemistry‐activity relationship of ceramide‐induced exosome production to clear amyloid‐β in Alzheimer's disease

“…As sphingosine has two asymmetric stereocenters at C2 and C3, there is an erythro enantiomeric pair (D-erythro sphingosine: DE and L-erythro sphingosine: LE) and a threo enantiomeric pair (D-threo sphingosine: DT and Lthreo sphingosine: LT). 29 The four diastereoisomers of sphingosine with four different tails (Figure 1) were synthesized as previously described with minor modifications [30][31][32] (Scheme S1). The procedure starts with methyl esterification of D-and L-serine, followed by Boc protection of the amino group and acetal protection of the primary hydroxyl and secondary amino groups to yield fully protected D-and L-serine.…”

Stereochemistry of Sphingolipids in Ganglioside GM3 Enhances Recovery of Nervous Functionality

“…Initially, three other sphingosine stereoisomers were prepared from l - or d -serine according to a slight modification of a well-established method (Scheme S1). Stereoisomeric sphingosines 1 were acylated with stearic acid in a standard manner to afford ceramides 2 . Subsequently, the primary alcohol in 2 was selectively protected with trityl group 3 , followed by secondary alcohol protection with benzoyl group 4 and detritylation to afford ceramide derivatives 5 in moderate yield (Scheme ).…”