Hydroxypropyl substituent

The presence of the two spirotetrahydrofuran rings in these reactive intermediates is obviously not condudve to the stereocontrolled synthesis of 14. This problem was resolved by making recourse to 22, a precursor to 15, the silyl-protected (3-hydroxypropyl) substituent which was viewed to be sufficiently bulky to guarantee its equatorial occupancy in the lowest energy conformation (Scheme 3-4). Furthermore, treatment of 22 with Grignard reagent should be met with rapid deprotonation of the hydroxyl and formation of chelate 23. At this point, customary equatorial... 

Fluoro-3-iodopyridine 212 was used by Comins and Saha as the starting material in a synthesis of mappicine. The first-formed organolithium 213 rearranges to 214 and a quench gives 215. Iodine-lithium exchange allows introduction of the C-4 hydroxypropyl substituent of 216 (Scheme 104). 

Halohydrin formation with subsequent reductive dehalogcnation represents an interesting variation on the theme. For example, when the enone rac-1 was treated with A -bromosuccin-imide in aqueous dimethyl sulfoxide, the bromohydrin roc-2 was formed, predominantly as one diastereomer (the relative configuration at C-3 was not established)23. Reduction with tri-butyltin hydride gave the diastereomeric products exo-3 and endo-3 in 27% and 63% yield, respectively. Here, the product distribution can be explained by the preferred attack of the hydride reagent on the exo-face of the intermediate bicyclic carbon radical, i.e., by kinetic control. Thus, the predominant endo-orientation of the 2-(2-hydroxypropyl) substituent at C-3 was achieved, in contrast to what may be expected from a reversible, i.e., thermodynamically controlled, hydration of the enone rac-1. 

The hydroxypropyl substituent, being larger yet, appears to require a lower DS to improve binding without sterically obscuring the cavity entrance. Muller and Brauns have studied the effect of the DS on complex-ing ability (Table 3) and have observed that lower degrees of hydroxypropyl substitution (2 to 5) are more conducive to complexation. As the DS increases, the solubilization of six different drugs decreases but when the DS is from 4 to 8 the solubilization is fairly consistent. 

A purified form of cellulose is reacted with sodium hydroxide to produce a swollen alkali cellulose that is chemically more reactive than untreated cellulose. The alkali cellulose is then reacted with propylene oxide at elevated temperature and pressure. The propylene oxide can be substituted on the cellulose through an ether linkage at the three reactive hydroxyls present on each anhydroglucose monomer unit of the cellulose chain. Etherification takes place in such a way that hydroxypropyl substituent groups contain almost entirely secondary hydroxyls. The secondary hydroxyl present in the side chain is available for further reaction with the propylene oxide, and chaining-out may take place. This results in the... 

A concise synthesis of lycopladine, an unusual and modestly cytotoxic lycopodium alkaloid, illustrates the remarkable ability of this reaction to introduce a carbon substituent at a crowded centre (Scheme 9.62). By virtue of hydroboration-oxidation, the hydroxypropyl substituent can be introduced via allylation. The central five-membered ring can be constructed by sequential conjugate addition and enolate coupling (see Section 2.11). 

Stemokerrin (59) was isolated from the roots of 5. kerri (HG 889) and its relative configuration was firmly established by X-ray crystallography, which revealed the pyrido[l,2-n]azepine substructure and the Z configuration of the double bond at C12-C13, which is also present in other Stemona alkaloids, such as protostemonine (19) and stemofoline (48) (56). The presence of a 1 -hydroxypropyl substituent (or its O-methyl derivative) attached to C4 is another distinct feature of this group of Stemona alkaloids [except for stemocurtisine (58)]. Comparison of the C-NMR data of stemocurtisine (58)... 

Condensation of the TV-substituted p-aminocrotonic acid ester 15 with p-benzoquinone (4) has been successfully carried out to furnish the 5-hydroxyindole 29 when the substituent R on the nitrogen of the aminocrotonic acid ester was methyl, ethyl, -propyl, isopropyl, or -butyl, -hexyl, p-cyanoethyl, p-hydroxyethyl, carbethoxymethyl, benzyl, phenyl, o-tolyl, dimethylaminopropyl, y-hydroxypropyl etc ... 

The main polymers used as thickeners are modified celluloses and poly(acrylic acid). Several different modified celluloses are available, including methyl-, hydroxypropyl methyl-, and sodium carboxymethyl-cellulose and their properties vary according to the number and distribution of the substituents and according to relative molar mass of the parent cellulose. Hence a range of materials is available, some of which dissolve more readily than others, and which provide a wide spread of possible solution viscosities. Poly(acrylic acid) is also used as a thickener, and is also available in a range of relative molar masses which give rise to give solutions of different viscosities. 

Pyrimido-fused purines can be prepared by intramolecular cyclization of A -(3-hydroxypropyl)guanines, a reaction similar to that of Equation (202). This cyclization can be achieved either via the mesylate <1997JME3248> or (presumably) by conversion of the hydroxyl substituent to chloro (Equation 204) <2001CPB188, 2002JME3440>. 

N-(2-Hydroxypropyl)carbamates (8.139, Fig. 8.13,b) are prodrugs that resemble the A-(2-hydroxyphenyl)carbamates discussed above. Here, activation yielded the tranquilizer mephenoxalone (8.140, Fig. 8.13,b) and an alcohol or a phenol such as paracetamol. Other active oxazolidinones could be obtained by replacing the MeO group in 8.139 (Fig. 8.13, b) with another substituent. For this series, the mechanism of activation is not an intramolecular nucleophilic attack, but, rather, decomposition of the deprotonated carbamate group as shown in Fig. 8.7,b, Reaction b, with the intermediate isocyanate being trapped to form the oxazolidinone ring. 

Richardson, S., Nilsson, G. S., Bergquist, K., Gorton, L., Mischnick, P. (2000). Characterisation of the substituent distribution in hydroxypropylated potato amylopectin starch. Carbohydr. Res., 328, 365-373. 

Hydroxyalkylcellulose. Reaction of cellulose with ethylene or propylene oxides produces hydroxyethyl or hydroxypropyl derivatives. By forming the hydroxyethyl derivative about the same ratio of hydrogen bonding sites to carbon atoms is provided as in the underivatized cellulose, but the substituent groups reduce the fit between polymer chains so that the derivative can be dissolved in water to produce stable solutions. The cellulose derivative has many of the solution properties of guaran. 

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