302 Subject Targeting molecules

Covalent synthesis of complex molecules involves the reactive assembly of many atoms into subunits with aid of reagents and estabUshed as well as innovative reaction pathways. These subunits are then subjected to various reactions that will assemble the target molecule. These reaction schemes involve the protection of certain sensitive parts of the molecule while other parts are being reacted. Very complex molecules can be synthesized in this manner. A prime example of the success of this approach is the total synthesis of palytoxin, a poisonous substance found in marine soft corals (35). Other complex molecules synthesized by sequential addition of atoms and blocks of atoms include vitamin potentially anticancer KH-1 adenocarcinoma antigen,... 

Dioxabicyclo[2.2.1]heptane naturally assumed the role of the principal target molecule. It represented a considerable synthetic challenge, for not only is it a strained bicyclic molecule containing the weak and labile 0—0 bond, but it is also a di(secondary-alkyl) peroxide which is the most difficult type to make by classical procedures 12). New synthetic methods of exceptional mildness were clearly needed to solve this problem. In the course of the development of such techniques and from a desire to establish their scope, a variety of saturated bicyclic peroxides have been obtained in addition to 2,3-dioxabicyclo[2.2.1]heptane. The question of how substitution patterns and ring sizes affect the reactivity of bicyclic peroxides has further served to broaden interest in the subject. 

Traditionally, amino acids have been utilized in the mainstream of organic chemistry primarily as building blocks for peptide syntheses. One may expect that in the future the use of amino acids as starting materials for non-peptide compounds will be a subject of ever-increasing interest. Many chiral target molecules with widely variable structures will be prepared from amino acids in the future. 

Chemists from the Sankyo Co. reported the use of 6-bromopenicillanate 28, easily obtained from 6-aminopenicillanic acid, in a multistep synthesis of (3RAR)-4-acetoxy-3- (R)- -((/-hutyldimethylsilyl)oxy)ethyl]-2-azctidinonc (31)97, a pivotal intermediate for the synthesis of 1-/9-methyl carbapenem antibiotics (equation 23)98. After cleavage of the thiazolidine ring of 28 with trimethyloxonium tetralluoroborate, the intermediate 29 was subjected to a Reformatsky condensation with acetaldehyde, catalysed by diethyla-luminium chloride. The 8-(S) stereocentre in 30, formed in 50% d.e., was inverted under Mitsunobo conditions to approach the target molecule 31. 

Covalent synthesis of complex molecules involves the reactive assembly of many atoms into subunits with aid of reagents and established as well as innovative reaction pathways. These subunits are then subjected to various reactions that will assemble the target molecule. Very complex molecules can be synthesized in this manner. 

The lysosomal enzymes The lysosomes are membrane vesicles ubiquitous to mammalian cells and contain a panoply of hydrolytic enzymes, estimated to be over 60 in number, that function to digest practically any biological macromolecule. They are important to the discussion of oral macromolecular drug delivery for two reasons. First, any macromolecules that escape digestion by the pancreatic and brush border enzymes are likely to be taken up into the epithelial cells by the process of endocytosis. In this process, the apical membrane invaginates and the target molecules enter endocytic vesicles that then fuse with the lysosomes and are subjected to intracellular hydrolysis by the lysosomal enzymes. Second, the sloughing-off of the epithelial cells means that the lysosomal enzymes will be released into the lumen of the intestine. They may be... 

During the convective transport individual target molecules are dispersed by the presence of small eddies. The random walk motion of small particles suspended in a fluid due to bombardment by molecules obeys the Maxwellian velocity distribution. If a number of particles subject to Brownian motion are present in a given medium and there is no preferred direction for... 

A retrosynthetic analysis may well lead to a molecule recognizably derived from the chiral carbon pool. Presumably, the resulting synthesis will then be subject only to the vagaries encountered in the preparation of any target molecule, chiral or not. Unfortunately, the actual situation is not always that simple. If the target molecule contains more than one chiral center, the introduction of the later centers must be highly stereoselective to avoid diastereomer formation. As noted above, though, diastereomers usually are separated fairly readily and the loss of a small amount of... 

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