Octane hydroxylation

The efficiency of n-octane hydroxylation was optimized and a mutant called variant 139-3 was found to perform this oxygenation 38 times faster than the wild-type enzyme. This variant is also very active for other substrates such as propane, hexane, cyclohexane, heptane, nonane and decane. Even ethane can be hydroxylated selectively with this engineered biocatalyst [121]. First reports on the control of... 

TA belong to a class of small molecules characterized by a derivatized tropane ring skeleton (8-methyl-8-azabicyclo[3.2.1]octane). Hydroxylated tropane (tropine) is esterified with diverse organic acids often representing structural analogues of, e.g. tropic, benzoic or mandelic acid (Fig. 1). Manifold variations are found either in natural sources or as (semi-) synthetic active pharmaceutical ingredients (API) with individual optimized properties. 

Contained within intermediate 25 is an acid-labile mixed acetal group and it was found that treatment of 25 with camphorsulfonic acid (CSA) results in the formation of dioxabicyclo[3.3.0]octane 26 in 77 % yield. Acid-induced cleavage of the mixed cyclic acetal function in 25, with loss of acetone, followed by intramolecular interception of the resultant oxonium ion by the secondary hydroxyl group appended to C leads to the observed product. Intermediate 26 clearly has much in common with the ultimate target molecule. Indeed, the constitution and relative stereochemistry of the dioxabicyclo[3.3.0]octane framework in 26 are identical to the corresponding portion of asteltoxin. 

Hydroxylation of n-octane by cell extracts of Gordonia (Corynebacterium) sp. strain 7E1C (Cardini and Jurtshuk 1968), and of some strains of Acinetobacter calcoaceticus induced with -hexadecane (Asperger et al. 1981). 

Epoxides may be formed from alkenes during degradation by Pseudomonas oleovorans, although octan-l,2-epoxide is not further transformed, and degradation of oct-l-ene takes place by co-oxidation (May and Abbott 1973 Abbott and Hou 1973). The co-hydroxylase enzyme is able to carry out either hydroxylation or epoxidation (Ruettinger et al. 1977). 

The hydroxylation of octane and cyclohexane catalyzed by Ti-MMM-1, a mixed- phase material (TS-1 and Ti-MCM-41) containing both micro- and mesopores, with aqueous H202 was reported by Poladi et al. (223). Ti-MMM-1 was found to be more active and selective in these hydroxylations than either Ti-MCM-41 or TS-1 the yield of alcohol was higher (Table XXVII). 

We optimized the growth of strain HXN-200 on n-octane and produced the cells in a large amount. It was found that the cells can be stored at — 80°C for two years without significant loss of activity. The frozen/thawed cells, that are easy to handle for the organic chemist, can be used for routine hydroxylation in an organic chemistry laboratory. 

It has been shown" that isomerization of the exocyclic allylic system of the five-membered ring D of kaurenols depends on the orientation of the C(15) hydroxyl group. The total synthesis of methyl atis-16-en-19-oate, a tetracyclic diterpenoid possessing a bicyclo[2.2.2]octane skeleton, has been accomplished" using a homoallyl-homoallyl radical rearrangement process of methyl 12-hydroxykaur-16-en-19-oate monothioimid-azolide (280) as the pivotal step. Two plausible mechanisms have been presented" ... 

This enzyme [EC 1.14.15.3], also known as alkane 1-monooxygenase, lauric acid ca-hydroxylase, fatty acid hydroxylate fatty acids in the [Pg.47]

Table 11. Catalytic hydroxylation of n-octane, 1-hexene and phenol with aqueous H2O2...

The activity data confirm that an IR absorption band at 960 cm" is a necessary condition for titanium silicates to be active for the selective oxidation of hydrocarbons with aqueous H2O2 as suggested by Huybrechts et al. (9). However, this band is not a sufficient condition for predicting the activity of the TS-1 catalyst. Although TS-l(B) and TS-l(C) show intensities for the 960 cm- band similar to TS-1 (A), their activities are different First of all, the reaction data reveal that TS-1 (A) is much more active than TS-l(B) for phenol hydroxylation, while both samples show similar activity for n-octane oxidation and 1-hexene epoxidation. Therefore, the presence of the IR band at 960 cm-i in TS-1 catalysts may correlate with the activities for the oxidation of n-octane and the epoxidation of 1-hexene but not for phenol hydroxylation. However, note that the amorphous Ti02-Si02 also has an IR absorption band at 960 cm- and it does not activate either substrate. 

In 1999 Uemuraetal. isolatedattenol A (100) and B (101) (Fig. 1.2.5), both marine natural products exhibiting a moderate cytotoxicity against P388 cells [57], from the Chinese Pinna attenuata. Since they are isomeric triols they differ only in the hydroxyl groups involved in the formation of the ketal functionality, so that this results in a l,6-dioxaspiro[4.5]decane and a 6,8-dioxabicyclo[3.2.1]octane unit as the main structural feature of attenol A and B, respectively. 

Fig. 6. Experiments concerning the P450-catalyzed hydroxylation of n-octane...

Site-specific saturation at key residues, followed by a high-throughput activity assay, produced the triple mutant F78V/L188Q/A74G, which shows a greatly increased 700-fold efficiency for the hydroxylation of w-octane and a 200-fold increase in the hydroxylation of [i-ionone at the 3-position [114], Stereoselectivity is poor, however, and all diastereomers are present in the products in comparable amounts. A five-fold mutant, the so-called (F87V)LARV, was developed in a related fashion [115] and shown to hydroxylate capric acid, a substrate not attacked by the wild-type enzyme [116]. 

Five generations of mutagenesis ra-Octane, ra-hexane, cydohexane, n-pentane (hydroxylation) [133], benzene, styrene, cydohexene, 1-hexene (epoxidation) [134]... 

Silver nitrate displayed a pronounced effect on the selectivity of silylation [380, 392, 440, 441], The treatment of uridine (63) with 2.2 molar equiv. of each fm-butylchloro-dimethylsilane and silver nitrate in oxolane led to the exclusive formation of 5 -0-silyl derivative 64 in 95% isolated yield [380], Under analogous conditions, 1,2-0-isopropylidene-ct-D-glucofuranose was selectivity silylated at 0-6, and 1,2-0-isopro-pylidene-oc-D-xylofuranose at 0-5, with 94-96% yield [442]. Combination of silver nitrate with pyridine resulted in disilylation of nucleosides at 0-5 and 0-2 with excellent selectivity. Interestingly, the selectivity for secondary hydroxyl groups is reversed with a combination of silver nitrate and l,4-diazabicyclo[2.2.2]octane as a base. Such a disilylation led to 3, 5 -6 -0-(/ert-butyldimethylsilyl) derivatives in as high yields as 94%. Other soluble silver salts, e.g., silver perchlorate, behaved similarly [380],... 

---