6a-methyl

The isolation of the 6-deoxytetracyclines (44) led to other chemical modifications of (1). 6P-Deoxytetracycline [5614-03-9] (13), prepared by catalytic hydrogenolysis of tetracycline (1), resulting ia an iaversion (45) of the configuration at the C-6 position, but retention of antibacterial activity. Catalytic reduction (7,8) of the 6-methylene derivative (14) yields both the 6a-methyl (15) and 6P-methyl compound (13). The 6a-isomer (15) is reported (7,45) to be more active than the 6P isomer (13). The a-isomer, doxycycline (6), is an example of a semisynthetic tetracycline that has become commercially useful. 

A -Acetyl-6A -methyl-L-leucine amide [32483-15-1] M 186.3. Recrystd from EtOH/hexane mixture. 

Reaction of methylmagnesium halide with the 6-ketones (26), (27) and (28) yields the 6a-methyl-6/ -hydroxy compounds. 

This sequence of steps has been used to prepare a large number of 6a-methyl-3-keto-A" -steroids in the estrane/ androstane " and preg-nane " " series. 

With saturated 6/ -hydroxy compounds containing only acetylated hydroxyl groups, 6/5,19-ethers are formed in 70-90% yield. " In the case of 5a-chloro-6a-hydroxy steroids up to 67% yield of 6/ ,19-ethers have been obtained, whereas with 6/5-hydroxy-3,20-diketals, yields are in the order of 10-20%. 6/5,19-Ethers are only formed in low yield from 6a-methyl-6/5-hydroxy steroids because of extensive eleavage of the 5,6-bond. In one case at 46% yield of crude ether was claimed. ... 

On the other hand the acetolysis of the 6y5,19-ether bridge is a useful reaction in the 6a-methyl-6j9,19-ether series ... 

The inclusion of a 6a-methyl group is known to potentiate the effect of progestins. Dlmethistarone represents an appllca-... 

Chemical Name 17/3-hydroxy-6a-methyl-17-(1-propynyl)androst-4-en-3-one Common Name —... 

Dehydro-6a-methyl-9a-fluorohydrocortisone Methanesulfonyl chloride Sodium iodide Sodium thiosulfate... 

Fractions 11 through 24 inclusive were combined, evaporated and twice recrystallized from acetone to give pure 6a-methyl-9a-fluoro-11(3,17a-dihydroxy-1,4-pregnadiene-3,20-dione of melting point 292° to 303°C. 

Preparation of Ba-Methyi-17-Hydroxy progesterone 17-Acetate 1 g of 6a-methyl-17a-hy-droxyprogesterone was dissolved in a mixture of 10 ml of acetic acid and 2 ml of acetic anhydride by heating. After solution was effected the mixture was cooled to 15°C, and 0.3 g of p-toluenesulfonic acid was added. After allowing the mixture to stand for a period of 2 /a hours at room temperature, the pink solution was poured into ice water to give an amorphous solid which was recovered by filtration. 

The precipitate was washed carefully with water and was then dissolved in 10 ml of methanol and 1.5 ml of methylene chloride. The solution was concentrated to 10 ml, diluted with 0.5 ml of 10% sodium hydroxide, boiled for one minute and cooled. The product, which crystallized on cooling, was recrystallized to give flakes of 6a-methyl-17a-hvdroxy-progesterone 17-acetate, having a MP 205° to 209°C, according to U.S. Patent 3,147,290. 

FIGURE 9 Moderately rapid gradient separation. Column XTerra MS C, IS, 4.6x 20mm 3.5p.m. Gradient 0 to 100% B over 4min,A 0.1% formic acid in water, B 0.1% formic acid in acetonitrile. Flow rate 3.0mL/min. Temperature 30°C. Detection UV at 254 nm. Instrument Alliance 2795 with 996 photodiode array detector. Compounds (I) acetanilide, (2) triamcinolone, (3) hydrocortisone, (4) 2-amino-7-chloro-5-oxo-5H-[l]benzopyrano[2,3-b]pyridine-3-carbonitrile, (5) 6a-methyl-17a-hydroxyprogesterone, (6) 3-aminofluoranthene, (7) 2-bromofluorene, (8) perylene, (9) naphtho(2,3-a)pyrene. 

Fiessdmann and Pfeiffer" passed HCl at 0° through acetoacetic ester and thioglycolic ester in dcohol to obtain triethyl y3, -bis(carbo-methoxymethylthio)butyrate (169) Dieckmann condensation reportedly furnish ethyl 3,4-dihydroxy-6a-methyl-3a,6a-dihydro-thieno(2,3-b]-thiophene-2-carbOxylate (170) [Eq. (48)]. 

System (2) has been employed for the determination of cortisol and cortisone in urine [150]. Urine containing 6a-methyl prednisolone as an internal standard was applied to a Sep-Pak Cig cartridge, eluted with aqueous 90% acetonitrile, and the eluent analyzed by HPLC. The analytical column (25 cm x 4.6 mm) is packed with Altex Ultrasphere C s bonded silica (5 pm), and requires the use of a (5 cm x 5 mm) Hypercil ODS (5 pm) pre-column. The mobile phase used gradient elution with less than 100% acetonitrile, and detection is by UV absorbance at 260 nm. 

In an early study Turpeinen and Stenman [99] published a negative-ion MRM ES-MS/MS method for urinary cortisol. The internal standard used was 6a-methyl-prednisolone and manual extraction was employed. Both steroids eluted within 6 min from the microbore column, but the total run and equilibration time was not reported. The transitions monitored were m/z 361—>331 for cortisol and m/z 373—> 343 for internal standard. The sample size was 1 ml. 

A variety of functional groups as well as conjugated and nonconjugated double bonds in the A-B-C-ring system of the steroid nucleus may be present during the addition of diazomethane to the A16-20-keto system. Compounds with the following partial structures have been examined 3/ -acetoxy-A5 3/ -hydroxy-A5 3-keto-A4 188 3/ -acetoxy-5cr-H 190 3/ -acetoxy-6-methyl-A5 191 6a-methyl-3-keto-A4 3-methoxy-19-nor-A1,3 5(10) 192 3a-acetoxy-l 1-keto-5/3-H 193-195 3/ -acetoxy-l l-keto-5a-H 196 3/ -acetoxy-5a-H-A9C11) 197 and 3>keto-A4,9(11).198... 

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