2- Amino-7-lactones, synthesis

The synthesis of a local anaesthetic required amino lactone (56) as intermediate. The amino groups could be made from a ketone, but if we use a nitro group instead (57) a reverse Michael disconnection gives a simple condensation product (58). 

Amino acid synthesis.1 Optically pure amino acids can be prepared in two steps from serine, readily available as either the d- or L-enantiomer. Reaction of N-benzylserine (or of N-benzyl-N-Boc-serine) with the preformed Mitsunobu reagent in CH3CN at -55° provides the protected serine (J-lactone (2) in almost quantitative yield. The lactone reacts with lithium organocuprates (R2CuLi) to... 

There has been a continuing interest in syntheses of 3-amino-2,3,6-trideoxy-hexoses such as daunosamine (9), acosamine (10), etc. In an interesting paper by Fronza et the two sugars have been synthesized from the non-carbohydrate compound (11), which was obtained in 25-30% yield from the incubation of cinnamaldehyde v th acetaldehyde in the presence of bakers yeast (Scheme 2). The crucial amino-lactone (12) was also synthesized from L-threonine. The same authors have also completed their synthesis of A-benzoyl-L-ristosamine (3-benzamido-2,3,6-trideoxy-L /6o-hexose) from 3-benzamido-2,3,6-trideoxy-L-xy/o-hexono-1,5-lactone (Vol. 13, p. 79). An alternative synthesis of methyl A-acetyl-a-L-acosaminide (13) has been described by reduction of the appropriate acetylated oxime by diborane. The thioglycoside (14) was also prepared. ... 

The validation of such hypothesis employing 111 as electrophile and furans, thiophenes, butenolides, and tertiary amino lactone equivalent as nucleophiles enabled the synthesis of all desired products with high level of stereocontrol (99% ee) (Scheme 2.32). 

A large number of nuclear analogues of the cephalosporin ring system have been synthesised and comprehensively reviewed (46, 155, 156). Approaches to the natural products themselves have been limited. The Roussel (157) and Squibb (158) groups have utilised suitably protected intermediates of type (184) to make the amino acid (185). Cyclisation as in Sheehan s penicillin synthesis followed by deprotection afforded the amino lactone (186). 

The diversity of the Ugi-MCR mainly arises from the large number of available acids and amines, which can be used in this transformation. A special case is the reaction of an aldehyde 9-26 and an isocyanide 9-28 with an a-amino acid 9-25 in a nucleophilic solvent HX 9-30 (Scheme 9.5). Again, initially an iminium ion 9-27 is formed, which leads to the a-adduct 9-29. This does not undergo a rearrangement as usual, but the solvent HX 9-30 attacks the lactone moiety. Such a process can be used for the synthesis of aminodicarboxylic acid derivatives such as 9-31 [3, 30],... 

A direct catalytic conversion of esters, lactones, and carboxylic acids to oxazolines was efficiently achieved by treatment with amino alcohols in the presence of the tetranuclear zinc cluster Zn4(0C0CF3)60 as catalyst, essential for condensation and cyclodehydration reactions. For example, the use of (5)-valinol allowed the easy synthesis of oxazolines 125 and 126 in satisfactory yields <06CC2711>. A one-pot direct preparation of various 2-substituted oxazolines (as well as benzoxazoles and oxadiazoles) was also performed from carboxylic acids and amino alcohols (or aminophenols or benzhydrazide) using Deoxo-Fluor reagent <06TL6497>. 

Initially PDPs were synthesized by stepwise polycondensation of linear activated depsipeptide [93]. In 1985, Helder, Feijen and coworkers reported the synthesis of PDPs by ROP of a morpholine-2,5-dione derivative (cyclic dimer of ot-hydroxy- and a-amino acid cyclodepsipeptide, cDP) [94, 95]. The ROP method gives an alternative type of PDP by homopolymerization and also allows the copolymerization with other monomers (lactones and cyclic diesters) including LA, GA, and CL to give a wide variety of functional biodegradable materials. The synthesis of PDPs as functional biomaterials has been recently reviewed [17]. 

A synthesis of C-glycosyl a-amino acids by formylaminomethylena-tion of 1,4-lactones has been described.1393... 

Starting from 5-O-acetyl-1,2-0-isopropylidene-a-D-glucofuran-urono-6,3-lactone, Kinoshita and coworkers178 achieved the synthesis of 3-amino-3-deoxy-l,2-0-isopropylidene-a-D-allofuranuronic acid by the following sequence of reactions methanolysis of the lactone ring, oxidation at C-3 to form methyl 5-0-acetyl-l,2-0-isopropyli-dene-a-D-riho-3-hexulofuranuronate, followed by stereospecific reduction of the oxime of the latter. 

Finally, the amino metabolites of the NMs have been synthesized by researchers and used as standards. These synthesis methods include reduction of NMs with hydrogen in the presence of Pd/charcoal to form the amino metabolites [ 15,16,23] or reaction of NMs with hydrazine hydrate and Raney nickel [ 14,23]. A metabolite of HHCB, HHCB-lactone, has also been synthesized and used as a standard [17]. 

Stereoselective allylation of aldehydes is another preferred strategy for the synthesis of appropriate intermediates for the total synthesis and introduction of hydroxy functionalities. Park and co-workers <2003S2473> proposed a synthesis of castanospermine 228 through a key indium-mediated allylation in the presence of (+)-cinchonine of an a-amino aldehyde 247 derived from D-glucono-O-lactone (Scheme 53). 

Asymmetric synthesis of amino acids.1 These lactones can serve as an optically active form of glycine for synthesis of either D- or L-amino acids. Thus (+ )-1 (or (—)-l) on radical bromination is converted into a single monobromide (2), which can be coupled with nucleophilic organometallic reagents, by either an SN1... 

Abstract Synthetically useful examples of carbonylations of aldehydes that enable the synthesis of structurally diverse carbonyl compounds such as -amino acids, -hydroxy carbonyl compounds, furanones, and lactones will be highlighted in this chapter. 

In order to decrease the number of chemical steps in the synthesis of l-[4- F]fluorophenylalanine, a potential marker for probing protein synthesis [140a], [4- F]fluorobenzaldehyde has been directly condensed with an imino-lactone. Hydrolysis then chiral HPLC yield the S amino acid in 5 % radiochemical yield (Scheme 33). 

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