Biomimetic Routes

Quideau, S. Ralph, J. A biomimetic route to lignin model compounds via silver(I) oxide oxidation. 1. Synthesis of dilignols and non-cyclic benzyl aryl ethers. Holzforschung 1994, 48, 12-22. 

P. Calvert and A. Broad, Biomimetic routes to magnetic iron oxide-polymer composites. In K.L. Mittal (Ed.), Polymers in Information Storage Technology, Plenum Press, New York, 1991, p. 257. 

Similarly to the above-mentioned entrapment of proteins by biomimetic routes, the sol-gel procedure is a useful method for the encapsulation of enzymes and other biological material due to the mild conditions required for the preparation of the silica networks [54,55]. The confinement of the enzyme in the pores of the silica matrix preserves its catalytic activity, since it prevents irreversible structural deformations in the biomolecule. The silica matrix may exert a protective effect against enzyme denaturation even under harsh conditions, as recently reported by Frenkel-Mullerad and Avnir [56] for physically trapped phosphatase enzymes within silica matrices (Figure 1.3). A wide number of organoalkoxy- and alkoxy-silanes have been employed for this purpose, as extensively reviewed by Gill and Ballesteros [57], and the resulting materials have been applied in the construction of optical and electrochemical biosensor devices. Optimization of the sol-gel process is required to prevent denaturation of encapsulated enzymes. Alcohol released during the... 

However, it has to be realized that biological templates remain inserted in the final nanoparticles and this is not acceptable for many applications. Nevertheless, some recent examples indicate that such biomimetic materials may be suitable for the design of biotechnological and medical devices [32]. For instance, it was shown that silica gels formed in the presence of p-R5 were excellent host matrices for enzyme encapsulation [33]. In parallel, biopolymer/silica hybrid macro-, micro- and nanocapsules were recently obtained via biomimetic routes and these exhibit promising properties for the design of drug delivery materials (see Section 3.1.1) [34,35],... 

Application to both Type I and Type II intramolecular Diels-Alder cycloaddition has also met with appreciable success, the most efficient catalyst for these reactions being imidazolidinone 21 (Scheme 7) [51, 52]. The power of the inttamolecular Diels-Alder reaction to produce complex carbocyclic ring structures from achiral precursors has frequently been exploited in synthesis to prepare a number of natural products via biomimetic routes. It is likely that the ability to accelerate these reactions using iminium ion catalysis will see significant application in the future. 

By using the same method, Katsumura and coworkers isolated the enantiomerically pure allene segment in 97a and 97b (Scheme 26)". The one-step singlet oxygen ene reaction pathway, to produce the allene moiety from the twisted l,3,3-trimethylcyclohexenyl-2-vinyl derivatives, was considered as a possible biomimetic route towards the synthesis of carotenoids. 

A comparison of siderophores that have been both totally biosynthesized and chemically synthesized reveals that the more structurally simple compounds (pyo-chelin, myxochelin) can be synthesized following a biomimetic route, whereas more complex molecules (yersiniabactin, enterobactin, vibriobactin) often tend to... 

The common intermediate in two published biomimetic routes to Lythraceae alkaloids was substituted 4-phenylquinolizid-2-one. In one approach based on a biogenetic hypothesis of Ferris et al. (62), Wrobel and Gol biewski condensed pelletierine (126) with isovanillin (128) and obtained a transfused quinolizidine derivative (130, jS H-5) (64) in 75% yield. A model condensation of pelletierine (126) with benzaldehyde which resulted in a mixture of quinolizidones was reported earlier by Matsunaga et al. (65). In another approach Rosazza et al. (52) condensed A -pjperideine (132) with /J-ketoester 133 to get 134. The next stage in both approaches was reduction of the ketone and esterification or transesterification with derivatives of p-hydroxycinna-mic acid (135 or 136). Investigations into the oxidative coupling of 137 were unsuccessful. 

An analogous biomimetic route to stizolobinic acid 15, the biosynthetic side chain precursor to acromelic acid A 5, was also carried out.23 Iron(III)-catalyzed peracetic acid cleavage of the catechol portion of 23 gave alanyl muconic acid 24 which was cyclized and concomitantly deprotected to (i)-stizolobinic acid 15 (Scheme 5). Use of Schollkopf bislactim ether methodology26 also allowed the formation of enan-tiomerically pure 15 by an analogous route. 

Snider BB, Neubert BJ (2004) A novel biomimetic route to the 3-acyl-5-hydro-xy-3-pyrrolm-2-one and 3-Acyl-3,4-epoxy-5-hydroxypyrrolidin-2-one ring systems. J Org Chem 69 8952-8955... 

A radical cyclization onto cross-conjugated quinone monoacetals provides a general approach to 5-hydroxydihy-drobenzoj/ jfurans upon aromatization with />-toluenesulfonic acid (Scheme 99) <2003GC526>. A biomimetic route to dihydrobenzofurans employs a dihydroquinone-mediated reductive cyclization of 2-hydroxyethyl-substituted quinone precursors <2001JOC4965>. 

Barton(29) devised a biomimetic route to thebaine (3), dihydrothebainone (13), and thus morphine following observations of Battersby.(30,3l) The alkaloid salutaridine (19) was derived from (+)-reticuline (18) by a low-yielding (0.03%) regioselective para-ortho phenolic coupling reaction according to Scheme 2.3. By the use of thallium tristrifluoracetate, Schwartz(32) improved yields to up to 23%. 

Before the biosynthetic studies, total synthesis of betaenone C (50) was completed through a biomimetic route as shown in Fig. 12 [40]. The synthetic strategy involving the intramolecular Diels-Alder reac-... 

This biomimetic route represents a convenient synthesis of small amounts of LTA4 and hence of LTC4, LTD4, and LTE4,but the reactivity of the peroxide intermediates would probably make scale-up difficult. 

Asymmetric reduction of ketopantoyl lactone is an effective biomimetic route to R-(- )-pantolactone, an intermediate in the synthesis of the important d-( + )-pantothenic acid (a component of vitamins B and of coenzyme A) ... 

The methyl ester 152 seems to be an important precursor for the total syntheses of oscillatoxin Ds. However the carboxylic acid corresponding to 152 could not be obtained under various conditions. Under the usual alkaline hydrolysis, isomerization occurred to the other stereoisomers and further led to decomposition of the substrate. Some nucleophilic deprotections in aprotic solvents or using Lewis acids were not effective, and mainly resulted in no reaction. Therefore, this route via 152 was suspended, and an alternative biomimetic route via an intermediate [C], as shown in Scheme 23, was carried out according to the initial retrosynthesis. 

Amanita musaaria.- A yellow pigment isolated from the fly agaric mushroom has been identified as the dihydroazepine (34) and its synthesis via a biomimetic route involved the conversion of 3-(2-carboxy-5-pyridyl)alanine to the glutaconic dialdehyde (35) and thence to (34). 

Lukianols A and B (49 and 50) were isolated from an unidentified ascidian collected at Palmyra atoll (N.E. of the Solomon Islands) [43]. Lukianol A exhibited moderate cytotoxicity (ICsoof 1 pg/mL against KB cell cultures), but lukianol B was 100 times less active [43]. The lukianols are closely related to polycitrins A and B (51 and 52), which were isolated from a Polycitor sp. [44]. Polycitrin A has been synthesised [45] by a proposed biomimetic route (based on known slime mould metabolites), but no activity data for the polycitrins has been published. These metabolites are some of the simplest of a group of highly substituted pyrrole derivatives... 

A biomimetic route for the synthesis of dihydrobenzo[b]furan heterocycles was investigated via a reagent-based electrochemical transformation of 2-(2 -hydroxyethyl)-quinine precursors. It was believed that a putative oxonium ion was generated by treatment of the quinone with PPTS, followed by reduction with dihydroquinone (DHQ) to generate a radical species which underwent either further reduction by DHQ to give the product or a direct dimerization <01JOC4965>. 

Ojima, I., Kogure, T. and Terasaki, S. (1978) Effective biomimetic route to D-(+)-pantothenate using asymmetric hydrogenation catalyzed by a chiral Rh complex in the key steps, J. Org. Chem. 43,3444-3446. 

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