Building block lactic acid

PLA can be produced by condensation polymerization directly from its basic building block lactic acid, which is derived by fermentation of sugars from carbohydrate sources such as com, sugarcane, or tapioca, as will be discussed later in this chapter. Most commercial routes, however, utilize the more efficient conversion of lactide—the cyclic dimer of lactic acid— to PLA via ring-opening polymerization (ROP) catalyzed by a Sn(ll)-based catalyst rather than polycondensation [2-6]. Both polymerization concepts rely on highly concentrated polymer-grade lactic acid of excellent quality... 

The metabolic pathways can be diverted to other products, however. For instance, the pyruvic acid can be rehydrogenated to lactic acid. Accordingly, glucose is converted into two molecules of lactic acid, which is the building block for Cargill s polylacate polymer [65],... 

Hydroxypropionic Acid (3-HPA). Like the structurally isomeric lactic acid, 3-HPA constitutes a three-carbon building block with the potential of becoming a key intermediate for a variety of high-volume chemicals malonic and acrylic acids, methacrylate, acrylonitrile, 1,3-propanediol, and so forth.Thus, Cargill is developing a low-cost fermentation route by metabolic engineering of the microbial... 

Hydrogen cyanide is an important building block chemical for the synthesis of a variety of industrially important chemicals, such as 2 hydroxy-4 methylthiobutyric acid, adiponitrile, nitrilotriacetic acid, lactic acid, and methyl methacrylate. The primary commercial routes to hydrogen cyanide are the reaction of methane and ammonia under aerobic (Andrussow Process) or anaerobic conditions (Degussa Process), or the separation of hydrogen cyanide as a by-product of the ammoxidation of propylene < ) The ammoxidation of methanol could represent an attractive alternate route to HCN for a number of reasons. First, on a molar basis, the price of methanol has become close to that of methane as world methanol capacity has increased. However, an accurate long term pricing picture for these two raw... 

More than a dozen biocompatible and biodegradable polymers have been described and studied for their potential use as carriers for therapeutic proteins (Table 13.5). However, some of the monomer building blocks such as acrylamide and its derivatives are neurotoxic. Incomplete polymerization or breakdown of the polymer may result in toxic monomer. Among the biopolymers, poly-lactide cofabricated with glycolide (PLG) is one of the most well studied and has been demonstrated to be both biocompatible and biodegradable [12]. PLG polymers are hydrolyzed in vivo and revert to the monomeric forms of glycolic and lactic acids, which are intermediates in the citric acid metabolic pathway. 

Asymmetric microbial oxidation afforded the (-)-epoxide which has been explored as a building block ring opening reactions with organometallic nucleophiles, and via Friedel-Crafts reactions have been reported. [226,227]. A non-biotransformative approach to this epoxide has also been described [228]. Copper(II)-catalysed oxidative hydrolysis (Eq. 72) affords a lactic acid analogue in high enantiomeric purity [229]. 

Chiral information was introduced through the C3-building block 5 derived from lactic acid. The remaining two siereogenic centers in the natural product were provided under substrate control in the course of a domino cyclization... 

These dendrimers expand the repertoire of polymers available for study. Current investigations are primarily limited to linear polymers that possess ill-defined solution structures and fewer hydroxyl groups for further modification. The introduction of biocompatible building blocks (e.g., glycerol and lactic acid) augments the favorable and already known physical properties of dendrimers. These properties are likely to facilitate the design of new materials for specific biomedical and tissue engineering applications. 

In the last two decades, chiral receptors containing amidic functions were designed almost exclusively for binding protected amino acids [49-57], oligopeptides [54,58], and lactic [59], tartaric [60,61] or camphoric acid derivatives [62]. Usually, chiral building blocks such as spirobifluorene [49, 60], binaphthalene [51,57],or amino acid chains containing macrocycles [52-56,58] were employed. An interesting receptor was synthesized via connection of the calix[4]arene moiety with an aza-crown derivative [61]. 

What is interesting, however, is some of the chemistry that is not present. For example, the petrochemical industry does not have a basic feedstock in the five-carbon area and thus we see few products derived from or based on five-carbon chemistry. Optical active compounds are also missing from the petrochemical-derived product list. For example, lactic acid is now made exclusively from glucose, with the reason being that the fermentation route provides stereochemical purity that is difficult to achieve from petrochemical building blocks. 

Figure 4.3 Lactic acid as a building block for chemical production...

Ray, W. C., and Grinstaff, M. W. 2003. Polycarbonate and poly(carbonate-ester)s synthesized from biocompatible building blocks of glycerol and lactic acid. Macromolecules, 36, 3557-3562. 

Biobased polymers from renewable materials have received increased attention recently. Lactate is a building block for bio-based polymers. In the United States, production of lactic acid is greater than 50,000 metric tons/yr and projected to increase exponentially to replace petroleum-based polymers. Domestic lactate is currently manufactured from corn starch using the filamentous fungus Rhizopus oryzae and selected species of lactic acid bacteria. The produced lactic acid can then be polymerized into polylactic acid (PLA) which has many applications (Hatti-Kaul et al., 2007). However, so far, no facility is built to use biomass derived sugars for lactic acid production. More research needs to be done to develop microbes using biomass derived sugars for lactate production. 

The third major source of chiral pharmaceuticals involves synthesis using naturally occurring chiral molecules as starting materials (5,17). Those compounds most generally used are carbohydrates, amiiu) acids, terpenes, and smaller, microbiologically derived compounds such as lactic acid or tartaric add. In addition, the synthetic chemist now has in his or her repertoire a variety of rather standard building blocks derived by manipulation of the natural substances a list of such compounds has been compiled (5). 

Recently, Steckhan and coworkers [485,486] have reported that anodic methoxyla-tion of chiral 5-methyl- and 5-chloromethyl-2-oxazolidinones followed by Lewis acid-catalyzed allylation provides 4-allyl products highly diastereoselectively. Similarly, anodic methoxylation of cyclic dipeptides and dipeptolides derived from chiral a-amino acid [487] or a-hydroxy acid [488] provides useful chiral synthetic building blocks, as in Eq. (64). a-Alkoxylation of lactic amide derivatives was also reported [489]. However, the diasteros-electivity was low. 

Production of (5)-2-chloropropanoic acid from racemic 2-chloropropanoic acid by enan-tioselective degradation of the R-enantiomer with whole cells of R-dehalogenase-contain-ing Pseudomonas putida. (5)-2-chloropropanoic acid is a building block for a wide range of herbicides and is produced by ICI (2000 tons per year). The side product (S)-lactic acid is also of commercial interest. 

Acetylenic diols, potential building blocks for the synthesis of L-hexoses and L-pentoses, are available with either syn or anti configuration using TBPS-protected L-lactic acid derivatives as the chiral source (Scheme 108). 

Ring opening of (5)-2-methyloxirane (Cf building block in Scheme 41), accessible from (5)-lactic acid [105]) by the Grignard compound of the C15 phenol derivative leads to the hydroxyalkyl-substituted phenol of Scheme 40. 

Before we can declare the photolactonization-based synthesis of lichen macrolide 100 a success, we need a reference case. One synthetic reference leading to 100, in which the complete set of stereogenic centers was introduced with no stereoselection, i.e., using chiral, nonracemic building blocks from the chiral C pool [107] (in this case D-mannose and D-lactic acid), was designed and carried out in Frankfurt, too Scheme 47). 

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