Synthesis of (+-)-2-Formyl-5-(hydroxymethyl)pyrrole-1-norleucine. A Biologically Active Maillard Reaction Product Derived from Glucose and Lysine.

Miller, Raya; Olsson, Kjell; Chattopadhyaya, J.

doi:10.3891/acta.chem.scand.39b-0717

Cited by 11 publications

(2 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The formation proceeds via nucleophilic attack of the ε-amino group of lysine at the C2-carbonyl moiety, followed by dehydration, cyclization and aromatization (Fig. 3) [38][39][40][41].…”

Section: Cyclizationmentioning

confidence: 99%

Pathways of the Maillard reaction under physiological conditions

2016

View full text Add to dashboard Cite

Initially investigated as a color formation process in thermally treated foods, nowadays, the relevance of the Maillard reaction in vivo is generally accepted. Many chronic and age-related diseases such as diabetes, uremia, atherosclerosis, cataractogenesis and Alzheimer's disease are associated with Maillard derived advanced glycation endproducts (AGEs) and α-dicarbonyl compounds as their most important precursors in terms of reactivity and abundance. However, the situation in vivo is very challenging, because Maillard chemistry is paralleled by enzymatic reactions which can lead to both, increases and decreases in certain AGEs. In addition, mechanistic findings established under the harsh conditions of food processing might not be valid under physiological conditions. The present review critically discusses the relevant α-dicarbonyl compounds as central intermediates of AGE formation in vivo with a special focus on fragmentation pathways leading to formation of amide-AGEs.

show abstract

“…The formation proceeds via nucleophilic attack of the ε-amino group of lysine at the C2-carbonyl moiety, followed by dehydration, cyclization and aromatization (Fig. 3) [38][39][40][41].…”

Section: Cyclizationmentioning

confidence: 99%

Pathways of the Maillard reaction under physiological conditions

2016

View full text Add to dashboard Cite

show abstract

“…This method, however, required the preparation of the key 3deoxyglucosulose intermediate (43% yield from glucose). 44 Additionally, alternative methods to synthesize pyrraline include multistep reactions reported by Miller and Olsson, 45 and Schußler and Ledl 46 which afforded pyrraline in an overall yield of 14% and 17%, respectively. Though several methods have been reported for the preparation of pyrraline, multiple purification procedures are often involved and the yields are moderate.…”

Section: ■ Synthesis and Incorporation Of Pyrraline Into Peptidesmentioning

confidence: 99%

Chemical Synthesis of Peptides Containing Site-Specific Advanced Glycation Endproducts

2016

View full text Add to dashboard Cite

In nature, proteins, lipids, and nucleic acids can nonenzymatically react with sugars and sugar degradation products to give rise to a diverse range of modifications, known as advanced glycation endproducts (AGEs). These AGEs typically occur at lysine and arginine residues of long-lived proteins, such as collagen, and can modify the structure and function of the native protein. AGEs accumulate during the normal aging process, and AGE formation is dramatically accelerated with diabetes. AGEs have also been implicated in a wide range of debilitating conditions including cardiovascular, renal failure, and neurodegenerative diseases. Thus, there is an ongoing interest in studying the role of AGEs in different aspects of these disorders. Typically, glycated proteins are prepared using nonspecific in vitro incubation techniques. However, this method results in a complex mixture of products which is then employed without further purification. In order to determine the effect of individual AGEs in a peptide sequence, in this Account, we highlight our synthetic methods for site-specifically introducing five frequently occurring AGEs, namely, N-(carboxymethyl)lysine (CML), N-(carboxyethyl)lysine (CEL), pyrraline, glyoxal-lysine dimer (GOLD), and methylglyoxal-lysine dimer (MOLD) into collagen peptides. Both a collagen model peptide (CMP) and the telopeptide region of human type I α1 collagen (CTP) were chosen due to being prone to glycation and cross-linking in vivo. For the preparation of the AGE-modified collagen peptides, we investigated both the initial preparation of AGE building blocks in solution followed by incorporation into Fmoc-SPPS, as well as an on-resin method whereby AGEs were selectively introduced by modification of the side-chain of an unprotected resin-bound lysine. Both of our synthetic methods enabled the site-specifically modified AGE-containing collagen peptides to be obtained in high purity and yield. In addition, the on-resin method had the added advantage of requiring fewer synthetic steps. We then evaluated the impact of the specific AGEs on the properties of the native protein and found that the AGE modifications protected against proteolytic digestion, enhanced copper binding at physiological pH, and, for the cross-linking AGEs, disrupted the triple helical structure of CMPs. Overall these synthetic methods offered a new strategy for preparing peptides site-specifically modified by AGEs, which can be applied to other peptidic systems, thereby enabling further insights into the biochemical consequences of AGEs.

show abstract

The Krapcho Dealkoxycarbonylation Reaction of Esters with α‐Electron‐Withdrawing Substituents

Krapcho

Ciganek

2013

Organic Reactions

View full text Add to dashboard Cite

The Krapcho reaction involves esters with α‐electron‐withdrawing substituents such as malonates, β‐keto esters, and α‐cyano esters, which undergo dealkoxycarbonylation on being heated in polar aprotic solvents (such as DMSO, DMF, or HMPT) in the presence of water, or in polar aprotic solvents with water in the presence of added salts (such as NaCN, NaCl, LiCl, LiI, or MgCl 2 ). This procedure avoids the use of strongly aqueous acidic and alkaline conditions and tolerates many functional and protecting groups. The chapter presents the mechanistic aspects of this procedure, which include reaction parameters such as solvents, salts, other additives, and the use of microwave irradiation. The diastereoselectivity of protonation of the enolate intermediate leading to the dealkoxycarbonylated products is discussed. Trapping of the intermediate enolate by electrophiles other than a proton is illustrated. Potential side reactions and same‐pot subsequent reactions of substrates are discussed along with functional‐group compatibility for halogens and nitrogen, oxygen, sulfur, selenium, and carbon functional groups. Several examples of applications of this methodology for the synthesis of natural products along with experimental conditions and procedures are presented. Closely related methods are discussed in the Comparison with Other Methods section. The tables, which consist of 371 pages, are grouped according to substrate structure. Selective entries for other methods (excluding classical aqueous acidic or basic methods) are included in the tabular survey for comparative purposes.

show abstract

Synthesis of (+-)-2-Formyl-5-(hydroxymethyl)pyrrole-1-norleucine. A Biologically Active Maillard Reaction Product Derived from Glucose and Lysine.

Cited by 11 publications

References 0 publications

Pathways of the Maillard reaction under physiological conditions

Pathways of the Maillard reaction under physiological conditions

Chemical Synthesis of Peptides Containing Site-Specific Advanced Glycation Endproducts

The Krapcho Dealkoxycarbonylation Reaction of Esters with α‐Electron‐Withdrawing Substituents

Contact Info

Product

Resources

About