Chiral steroidal acetal

Nitrophenyl)ethylene glycol was used to protect simple aldehydes and ketones, as well as some steroids. Acetals were prepared under acid catalysis, leading, in the case of chiral carbonyl compounds to diaste-reoisomers. The photochemical removal of the protecting group was in several instances complicated by the instability of some carbonyl derivatives to irradiation at 350 nm otherwise, yields were in the range of 83-90% (see Scheme 19). 

Deuterated and tritiated tin hydrides have been used to prepare deuterated saccharides93 and tritiated steroids46 from alkyl bromides, (equations 68 and 69). It is important to note that isomerization has occurred at the chiral reaction centre in the saccharide reaction (equation 68). For the steroid, the tin hydride reaction is regiospecific, i.e. it only reacts at the more reactive bromide rather than the less reactive chloride site and does not react with the keto group, the hydroxyl group or the acetal group. 

An asymmetric C-H insertion using a chiral 3,3, 5,5 -tetrabromosubstituted (salen)manganese(m) complex 107 with TsN=IPh afforded insertion products with ee up to 89%.258 Che reported the first amidation of steroids such as cholesteryl acetate with (salen)ruthenium(n) complexes 108.259... 

Chiral l,3-dioxin-4-ones photochemically react intermolecular with (cyclic) ethers, acetals, and secondary alcohols to give the addition products in reasonable yields. The radical addition was completely stereoselective at C-6 of the heterocycle <1999EJO1057>. The exocyclic diastereoselectivity, where relevant, was about 2 1 (Equation 30). In analogy, an intramolecular cascade reaction of a 1,3-dioxin -one derived from menthone was used to get a terpenoid or a steroid framework in optically active form <1997JA1129, 1999JA4894>. 

The number of investigations on the enantioselective dipolar cycloaddition of nitronates is still rather limited. In the case of simple alkyl nitronates, the facial selectivity is controlled solely by the steric environment about the two faces of the chiral unit. For example, the reaction of steroid dipolarophile 270 proceeds with the nitronate approaching the Re face of the alkene (Eq. 2.23) (234). The facial selectivity is controlled by the C(19) methyl group, which blocks the Si face of the dipolarophile. Similarly, exposure of 279 to ethyl acrylate at 40 °C for 24 h, provides a single nitroso acetal (Scheme 2.21) (242). The facial selectivity is presumed to arise from steric shielding by the menthol group, however the full stereostructure has not been established. 

The complexation of chiral dienes leads to the formation of diastereomeric j -diene iron tricarbonyl complexes. An early example was actually carried out for the protection of the diene unit found in the steroid B-ring of ergosteryl acetate (equation 53) neither the stereochemical assignment nor the diastereomer ratio were estabhshed. Similarly, the tricarbonyl iron complex of calciferol was also prepared. ... 

The seminal work on steroid analyses using chiroptical detection was done by Djerrasi by the determination of hecogenin acetate in the presence of tigonenin acetate.Every steroid is chiral and therefore amenable to polarimetric detection after chromatographic separation. Chromophores are fairly uncommon, and analysis by ORD or CD is therefore less suitable. The only unsaturation in the cholesterol molecule, for example, is the isolated A -double bond, which has an absorbance maximum at 205 nm. Unsaturation coupled with chirality provides some selectivity, as ably demonstrated by the work of Potapov for analogs of progesterone Even simpler than that is the direct discrimination between the ketosteroids testosterone and dihydrotestosterone, which have opposite signs in methylene chloride solution (Fig. 6). 

Ti complexes have been extensively used for the stereoselective introduction of side chains in steroidal molecules, e.g. pregnenolone acetate and the steroidal C-22 aldehyde (73 equation 29). In these cases satisfactory results are only obtained by using Ti reagents, like methyl, ds-methyl and allyl derivatives, due to the strong steric hindrance that affects the position to be attacked. 1,3-Anti dia-stereoselecdon in the addition of alkyltitanium reagents to chirally -substituted aldehydes having a dithioacetal group at the a-position (75) was also observed (equation 30). ... 

Steroids are members of a large class of lipid compounds called terpenes. Using acetate as a starting material, a variety of organisms produce terpenes by essentially the same biosynthetic scheme (Fig. 8). The self-condensation of two molecules of acetyl coenzyme A (CoA) forms acetoacetyl CoA. Condensation of acetoacetyl CoA with a third molecule of acetyl CoA, then followed by an NADPH-mediated reduction of the thioester moiety produces mevalonic acid [150-97-0] (72). Phosphorylation of (72) followed by concomitant decarboxylation and dehydration processes produce isopentenyl pyrophosphate. Isopentenyl pyrophosphate isomerase establishes an equilibrium between isopentenyl pyrophosphate and 3,3-dimethylallyl pyrophosphate (73). The head-to-tail addition of these isoprene units forms geranyl pyrophosphate. The addition of another isopentenyl pyrophosphate unit results in the sesquiterpene (C15) famesyl pyrophosphate (74). Both of these head-to-tail additions are catalyzed by prenyl transferase. Squalene synthetase catalyzes the head-to-head addition of two achiral molecules of famesyl pyrophosphate, through a chiral cyclopropane intermediate, to form the achiral triterpene, squalene (75). 

Cellulose can be esterified with acetic anhydride to form acetylated paper with hydrophobic properties [12], These papers, which are commercially available from Schleicher and Schiill with 5-40% of acetyl residues, serve for the reversed-phase chromatography of lipophilic substances such as steroids (13). It has been suggested that these papers are suitable for separation of racemic mixtures due to the migration of optical antipodes at different rates on the chiral acetyl cellulose [14]. 

A spectacular application of chiral acetals is in the biomimetic polyene cyclisation to give the steroid skeleton (106) made famous by Johnson. jjere no fewer than seven new stereogenic centres are created in one step. 

Also the observations of P. Planer [20] (1861) on the cholesteric phase of choleste-ryl chloride and by Reinitzer [21] (1888) on cholesteryl benzoate and acetate belong here, although in both cases chemical transformations had been undertaken on the natural products (chlorination esterification with acetic and benzoic acid anhydride, respectively) [22]. Also today nature is a source of mesogenic structures (steroids [23 a], triterpenes, carbohydrates [23b-d]) and of precursors of liquid-crystalline compounds (see sources of chirality). 

Acetoxypropanal, the hydroformylation product of vinyl acetate, can also be used in a Strecker a-amino acid synthesis to provide threonine, as well as being a source of chiral 2-hydroxypropanal, which is a very useful building block in the syntheses of steroids, antibiotics, and peptides For example, the potassium ionophore vali-nomycin, a dodecadepsipeptide that displays significant antibiotic activity, contains three chiral moieties derived from 2-hydroxypropanal. 

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