3S-1

Continued from Contents and Introduction

Contents

3S-1. General

1.0 Definition of steroids and sterols
1.1 Numbering and ring letters
1.2 Absent carbon atoms
1.3 Absolute configuration
1.4 Orientation of projection formulae
1.5 Stereochemistry of ring junctions and side-chain attachment
1.6 Stereochemistry of substituents in the side chain

3S-1.0. Definition of steroids and sterols

Steroids are compounds possessing the skeleton of cyclopenta[a]phenanthrene or a skeleton derived therefrom by one or more bond scissions or ring expansions or contractions. Methyl groups are normally present at C-10 and C-13. An alkyl side chain may also be present at C-17.Sterols are steroids carrying a hydroxyl group at C-3 and most of the skeleton of cholestane. Additional carbon atoms may be present in the side chain.

Note This definition of sterols is rather restrictive. However, a less restrictive definition would cause difficulties, e.g. androst-16-en-3-ol is normally not called a sterol and should not fall under the definition.

3S-1.1. Numbering and ring letters

Steroids are numbered and rings are lettered as in formula 1. If one of the two methyl groups attached to C-25 is substituted it is assigned the lower number (26); if both are substituted, that carrying the substituent cited first in the alphabetical order is assigned the lower number. For trimethyl steroids see Recommendation 3S-2.4, Note 2.

Note The numbers 28, 29 and 30 are now assigned to the additional methyl groups at C-4 and C-14 in triterpenoids, e.g. lanosterol (see 3S-2.4, Note 2). Therefore, the carbon atoms at the methyl or ethyl groups at C-24 had to be renumbered. The system adopted here allows also numbering of other carbon atoms attached to the steroid skeleton. If two side chains are attached to the same carbon atom, the shorter one receives primed numbers, e.g. 17^1' (see 3S-2.7, 3S-2.8 and addenda).

3S-1.2. Absent carbon atoms

If one or more of the carbon atoms shown in 1 is not present and a steroid name is used, the numbering of the remainder is undisturbed.

3S-1.3. Absolute configuration

The absolute stereochemistry of a steroid is defined by the parent name for some chiral centres (see 3S-1.5) and by , , R or S for other centres (see 3S-1.4 and 3S-1.6). When the configuration at one or more centres is not known, this is indicated by the Greek letter(s) (xi) prefixed by the appropriate locant(s).

3S-1.4. Orientation of projection formulae

When the rings of a steroid are denoted as projections onto the plane of the paper, the formula is normally to be oriented as in 2a. An atom or group attached to a ring depicted as in the orientation 2a is termed (alpha) if it lies below the plane of the paper or (beta) if it lies above the plane of the paper. In formulae, bonds to atoms or groups lying below the plane of the paper () are shown as broken lines(), and bonds to atoms or groups lying above the plane of the paper () are shown as solid lines (preferably thickened ). Bonds to atoms or groups whose configuration is not known are denoted by wavy lines().

Notes

(1) In the formula 2a given above, all angular methyl groups and H atoms have been written out explicitly. However, when there is no ambiguity, methyl groups may also be indicated by a bond without lettering as in 2b, a practice followed in other fields. Likewise, the hydrogen atoms at the bridgehead C-8, C-9 and C-14 may be omitted if there is no ambiguity, i.e. if they are oriented 8,9,14. If one of the hydrogen atoms is replaced, e.g. by a fluorine atom, care must be taken in the correct use of broken () and bold () lines. The bond to a bridgehead hydrogen atom should never be drawn without the H.

(2) Projections of steroid formulae should not be oriented as in formulae 2c, 2d or 2e unless circumstances make it obligatory, e.g.in dimers formed photochemically [4].

(3) With the preferred orientation 2a, and with 2c, which is only rotated in the plane of the paper, -bonds appear as broken lines and -bonds as solid (thickened) lines. The reverse is true for 2d and 2e; therefore, orientation 2c is preferred over 2d or 2e if there is a choice. Wavy lines denote -bonds for all orientations of the formula.

Example: 3,3'-Bicholesta-3,5-diene should be represented as 3a but not as 3b.

(4) A perspective representation of the stereochemistry of formula 2 as in 2f or 2g may also be used:

When steroid formulae are drawn in this way, bonds pointing upwards are, by convention, drawn bold and bonds pointing downwards are drawn broken; these representations correspond to the - and -bonds of projection formulae such as 2a and do not conform to the general practice that bold and broken lines denote bonds projecting respectively above and below the plane of the paper. Note, however, that the general practice is followed with chair and boat forms of spirostans (see Recommendation 3S-3.3).

(5) To save space and to emphasise the relevant portion of the steroid formula a brace may be used. For example 2h only shows ring D and the side chain at C-17 but in this context the portion to the left of the brace may be assumed to be the rest of an androstane ring system as in formulae 2a-g. In other contexts, for example, it might represent the rest of an estrane ring system, including any substituents, and double bonds present in that portion.

3S-1.5. Stereochemistry of ring junctions and side-chain attachment

Unless implied or stated to the contrary (see Recommendations 3S-3, 3S-4.1 and 3S-5), use of a steroid name implies that atoms or groups attached at the bridgehead positions 8, 9, 10, 13 and 14 are oriented as shown in formula 2a (i.e. 8,9,10,13,14), and a side chain attached at position 17 is assumed to be -oriented (see notes below). The configuration of hydrogen (or a substituent) at the bridgehead position 5 is always to be designated by adding , or after the numeral 5, this numeral and letter being placed immediately before the stem name. The stereochemistry of substituents attached to the tetracyclic systemA-D is stated by adding , or after the respective numerals denoting their position.

Notes

(1) If one of the bridgehead hydrogen atoms is replaced it may be desirable (although not necessary) to restate the stereochemistry, e.g.9-fluoro-5-pregnane instead of 9-fluoro-5-pregnane.

(2) For the purpose of this Recommendation, a carboxyl group at position 17 is treated as a substituent (see Recommendation 3S-4.1).

(3) If two carbon chains are attached at position 17, see Recommendations 3S-2.7 and 3S-2.8.

3S-1.6. Stereochemistry of substituents in the side chain

The stereochemistry of substituents on the steroid side chain is described by the sequence rule procedure (see [3], section E), unless implied by the name (see 3S-2.4 and Table 1). Examples:

Notes

(1) The backbone of a side chain at C-17 is best denoted as in the plane of the paper (lines of ordinary thickness), the 17-20 bond being similarly denoted.Stereochemistry due to substituents on the chain is then indicated by the customary thick or broken lines denoting bonds that project, respectively, above and below the plane of the paper. In formulae the representation of the side chain is drawn as in examples 6 and 7 in preference to those used in the previous edition of this document [1].

(2) In the pregnane series, the stereochemistry at C-20 was formerly designatedas 20 or 20. This convention was based on a Fischer projectionwith the highest number at the top, as given in formula 8. Thisnomenclature is now discouraged for specific compounds in favour of the R,S system, which can be generally used for all chiral centres in the side chain(s). However, as and are independent of substituents at neighbouring atoms they are retained for the corresponding enzyme names, e.g. 20-hydroxysteroid dehydrogenase.

1. IUPAC Commission on the Nomenclature of Organic Chemistry (CNOC) and IUPAC-IUB Commission on Biochemical Nomenclature (CBN). The Nomenclature of Steroids, Revised tentative rules, 1967. Arch. Biochem. Biophys. 136, 13-35 (1970), amended 147, 4-7 (1971); Biochem. J. 113, 5-28 (1969), amended 127, 613-616 (1972); Biochemistry, 8, 2227-2242 (1969), amended 10, 4994-4995 (1971); Biochim. Biophys. Acta, 164, 453-486 (1968), amended 248, 387-390 (1971); Eur. J. Biochem. 10, 1-19 (1969), amended 25, 1-3 (1972); Pure Appl. Chem. 31, 285-322 (1972), with amendments incorporated; also pp. 133-153 of [2], with amendments included.

2. International Union of Biochemistry (1978) Biochemical nomenclature and related documents, The Biochemical Society, London.

4. A. Butenandt and L. Poschmann, Ber. Dtsch. Chem. Ges. 73, 893-897 (1940); cf. also A. Butenandt, L. Karlson-Poschmann, G. Failer, U. Schiedt and E. Bilkert, Liebigs Ann. Chem. 575, 123-144 (1951).

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