Prenol nomenclature

These Recommendations were prepared by a panel whose members were W.L. Adair (USA), C.M. Allen (USA), T.W. Goodwin (UK), F.W. Hemming (UK, convenor), K. Ogura (Japan), J.F. Pennock (UK), T.W Porter (USA), H.C. Rilling (USA) and D.R. Threlfall (UK). They are as close as possible to the published version [see Eur. J. Biochem., 1987, 167, 181-184; J. Biol. Chem., 1988, 263, 601-604; Pure Appl. Chem., 1987, 59, 683-689; Biochemical Nomenclature and Related Documents, 2nd edition, Portland Press, 1992, pages 252-255; Copyright IUPAC and IUBMB; reproduced with the permission of IUPAC and IUBMB]. If you need to cite these rules please quote these references as their source. A PDF of the printed version is available.

Any comments should be sent to any member of the Committee

• Introduction
• General terms
  • Pr-1. Prenol
  • Pr-2. Polyprenol
  • Pr-3. Esters and their derivatives
  • Pr-4. Number of residues
• Stereochemistry
  • Pr-5. Double bonds
  • Pr-6. Order of stereochemical prefixes
  • Pr-7. Multiplicative prefixes
• Specilic compounds
  • Pr-8. Trivial names
  • Pr-9. Isopentenyl diphosphate
  • Pr-10. Relationship between polyprenols and isoprenoids
  • Pr-11. Juvenile hormones
  • Pr-12. Dolichols
• References

Present practice in the nomenclature of prenols takes little account of the important stereochemistry of these compounds. We therefore believe that a review of existing practice, with recommendations for specifing stereochemistry, should be helpful. Some of the recommendations have been used in Enzyme nomenclature [1].

General Terms

Pr-1. Prenol. The term prenol, already widely used (e.g. refs 2, 3, 5, 6), is recommended to describe the structure shown in formula I. It originated as a contracted name for isoprenoid alcohol (i.e. suffix -ol) [2].

The carbon atoms along the main chain are numbered from C-1, the atom that carries the hydroxyl group (C-15.11 of ref. 8). The methyl group carried by atom C-3 contains atom C-3¹, that carried by atom C-7 contains atom C-7¹, etc.

Note

This use of superscript numbers is based on section TP-2.1 of the recommendations for the nomenclature of tetrapyrroles [9]. In the printing of these recommendations in the European Journal of Biochemistry the relevant paragraph was accidentally transposed to the caption of Table 2.

The repeating C₅H₈ unit (inside the brackets of structure I) is termed an isoprene unit or an isoprene residue. Prenols and their esters are precursors of a variety of compounds, including terpenes and steroids, that have much of the carbon skeleton intact. Such compounds are known as isoprenoids.

Pr-2. Polyprenol. Polyprenols represent a subgroup of prenols. The term polyprenol, already widely used (e.g. ref. 2), is recommended for compounds of structure I in which n is greater than 4.

Pr-3. Esters and their derivatives. The terms prenyl diphosphate (or diphosphoprenol) and polyprenyl diphosphate (or diphosphopolyprenol), already widely used, are recommended for the esters of I with diphosphoric acid, and for the salts and anions of such esters. They are in accordance with recommendations for naming phosphorus-containing compounds [7].

Note

The term prenyl diphosphate is preferred to diphosphoprenol, because diphosphate has precedence over hydroxyl for being cited as suffix (C-10.3 of ref. 8).

Pr-4. Number of residues. The number of isoprene residues, i.e. the value of n in Formula I, in each molecule of a polyprenol or derivative should be indicated by a multiplicative prefix [10] instead of the general prefix poly- suggested in recommendation Pr-2, e.g. hexaprenol, heptaprenyl diphosphate.

Stereochemistry

Pr-5. Double bonds. The double bond in a residue is called cis or trans according to whether the main chain of the compound is cis or trans across that double bond. A residue containing a cis double bond may be called a cis residue, and one containing a trans double bond may be called a trans residue.

Note

The designations cis and trans refer to the configuration of the main chain across a double bond. Thus, unlike Z and E [11], they are independent of any substituents that may be present. This recommendation does not preclude the use of Z and E.

Pr-6. Order of stereochemical prefixes. The residue furthest from the hydroxyl group is referred to as the -residue, and stereochemical designations are given in order from the residue next to the -residue, ending with the residue that carries the hydroxyl group, e.g. ditrans,polycis-undecaprenol II).

Notes

1. The distinction between cis and trans forms does not exist for the -residue unless one of the two methyl groups is substituted. Therefore, stereochemical designators are given starting from the residue next to the -residue.

2. It is not advisable to omit stereochemical designations, as this can give ambiguity. Thus the name heptaprenyl diphosphate was applied [12] to the all-trans compound from a bacterium, but could be confused with ditrans,polycis-heptaprenyl diphosphate, which is found in silver birch and other plants [13]. The name undecaprenyl diphosphate was likewise applied [14] to the bacterial ditrans,polycis compound, which could cause confusion with the tritrans,polycis compound found in the leaves of higher plants [15].

3. Although large numbers of stereoisomers could arise if each newly added residue (Fig. 1) could be either cis or trans, the commonest prenols are confined to four main groups (Fig. 2), as follows: (i) all-trans-prenols, (ii) ditrans,polycis-prenols, (iii) tritrans,polycis-prenols, and (iv) all-cis-prenols. The symbols W, T and C that appear in Fig. 2, together with a fourth symbol S, provide a convenient set for representing polyprenol structures compactly as shown in Table 1.

Table 1

Symbol	Meaning
W	-residue
T	trans-residue
C	cis-residue
S	saturated (dihydro) residue

In group (i), the term 'all-trans' means that all the residues except the -residue have the trans configuration. In groups (ii) and (iii) the trans residues are grouped next to the -residue. Group (iv) is less well characterized, but probably exists as precursors of natural rubber.

4. The recommendation to cite stereochemical prefixes in the reverse order from their locants is contrary to normal recommendations. We make it because (1) it is already widely used, (2) it corresponds to the left-to-right order in most drawings of formulas and symbolic representations of prenols and their diphosphates, and (3) it names first the double bonds formed first in biosynthesis.

Example

all-trans-Nonaprenol is the plant product solanesol, which contains nine isoprene units, eight of which are trans, the ninth being the -residue.

Pr-7. Multiplicative prefixes. The prefix poly- may be replaced by an appropriate multiplicative prefix; e.g. the bacterial product bactoprenol can be called ditrans,octacis-undecaprenol rather than ditrans,polycis-undecaprenol.

Note

If this recommendation is followed it is not advisable to omit the multiplicative prefix indicating the total number of residues, even though it contains redundant information. In ditrans,octacis-undecaprenol, for example, a prenol with one , two trans and eight cis residues must have eleven residues in all.

Specific Compounds

Pr-8. Trivial names. Several short-chain prenols are known by trivial names. For example, the diphosphates with one to five residues are named as shown in Table 2.

Table 2

Fig. 1. The chain-lengthening step in prenol biosynthesis

Dimethylallyl diphosphate (strictly 3,3-dimethylallyl diphosphate), geranyl diphosphate and neryl diphosphate are entirely specified by name, and need no further stereochemical designation. Dimethylallyl is the trivial name for 3-methylbut-2-enyl. The name dimethylallyl does not conform to ref. 8, and is ambiguous if used outside biochemical contexts.

The name farnesyl diphosphate covers four C₁₅ stereoisomers. It is confusing that they have been designated trans,trans, cis,trans, trans,cis and cis,cis, with the first designator applying to C-2 and the second to C-6 [16], i.e. the reverse order from that used for polyprenols (recommendation Pr-6). We therefore recommend that locants should be used to minimize confusion, e.g. 2-cis,6-trans-farnesyl diphosphate; this becomes trans,cis when lengthened to form the -terminus of a polyprenol.

Two C₂₀ prenyl groups have been named geranylgeranyl and geranylneryl; in them the second isoprene residue from the oxygen atom is always trans, i.e. the group is 6-trans. The use of these terms is so widespread and well established that it would probably be damaging to recommend changes. Other compounds should be named according to sections Pr-4 to Pr-7, e.g. dicis,trans-tetraprenyl diphosphate for the compound with 2-trans-6,10-dicis stereochemistry.

Note

We see no harm in using the polyprenol system (sections Pr-4 to Pr-7) for C₂₀ compounds (i.e. naming them as tetraprenols). This usage eliminates the inconsistency of reversing the order of stereochemical designators for compounds of fewer than five residues.

Pr-9. Isopentenyl diphosphate. An important isomer of dimethylallyl diphosphate is isopentenyl diphosphate (structure III), the diphosphate of 3-methylbut-3-en-1-ol (isopentenyl alcohol). It is the universal building block of isoprenoids; a prenyl diphosphate reacts with it to lose diphosphate and grow longer by one residue (Figs 1 and 2). Its name should be retained.

Notes

1. The CH₂= group of isopentenyl alcohol contains C-4 [see recommendation C-13.11(b) of ref.8]. This is convenient, as C-4 of isopentenyl diphosphate is the precursor of C-4 of a lengthened prenol (Fig. 1).

2. The name isopentenyl is recommended only for biochemical use; it does not confonn to ref. 8 and is ambiguous outside biochemical and prenol contexts. Isopentenyl is the trivial name for 3-methylbut-3-enyl.

Fig. 2. Stereochemistry of polyprenol biosynthesis. Each arrow shows a transformation of the type given in Fig. 1. Upward sloping arrows represent trans additions of a unit from isopentenyl diphosphate (section Pr-9), and downward sloping arrows represent cis additions. An arabic numeral adjacent to an arrow indicates that an enzyme catalysing the reaction has been characterized and listed under that number in group EC 2.5.1 of Enzyme Nomenclature [1], e.g. EC 2.5.1.11 catalyses the conversion of geranyl-POP into trans,trans-farnesyl-POP. The groups given in the right-hand column refer to the main classes of polyprenols as listed in section Pr-6, note 3. Where locants are included the prefixes appear in locant order (section Pr-8), not in left-to-right order (section Pr-6). In the symbolic representation, W represents an -residue, T a trans residue, and C a cis residue.

Pr-10. Relationship between polyprenols and isoprenoids. The derived isoprenoids are named as listed in Table 3.

^a Triterpenoids are formed from squalene, which is derived from two farnesyl diphosphate precursor molecules.

^b Carotenoids are formed from phytoene, which is derived from two geranylgeranyl diphosphate precursor molecules.

Pr-11. Juvenile hormones. Farnesol is the prenol that corresponds to the carbon skeleton of the simplest juvenile hormone. Other members of this group of compounds have an ethyl instead of a methyl group at C-3 and/or C-7 and/or C-11. These may be specified as methyl-substituted farnesol derivatives where the stereospecificity of the -isoprene unit (where relevant) is indicated by which methyl group is substituted.

Examples

Pr-12. Dolichol. Dolichols are a group of prenol derivatives. The term, already widely used (e.g. ref. 2), is recommended for compounds of structure I in which n is greater than 4 and in which the residue that carries the hydroxyl group is saturated, i.e. 2,3-dihydropolyprenols. As dolichols are derivatives of prenols the collective terrn prenol should not be used without qualification to include dolichols.

References

1. Nomenclature Committee of the International Union of Biochemistry (1984) Enzyme nomenclature, 1984. Academic Press, Orlando, Florida.

2. Hemming, F. W. (1974) in Biochemistry, Series One, vol.4 (Goodwin, T. W., ed.) pp. 39-97, Butterworths, London.

3. IUPAC-IUB Commission on Biochemical Nomenclature (CBN). Nomenclature of quinones with isoprenoid side-chains. Recommendations, 1973. Biochem. J. 147, 15-21 (1975); Eur. J. Biochem. 53, 15-18 (1975); Pure Appl. Chem. 38, 441-447 (1974); also pp. 154-157 in ref. 4.

4. International Union of Biochemistry (1978) Biochemical nomenclature and related documents, The Biochemical Society, London. [Now as the 1992 edition]

5. Popják, G. & Cornforth, J. W. (1960) Adv. Enzymol. 22, 281-335.

6. Holloway, P. W. & Popják, G. (1967) Biochem. J. 104, 57-68.

7. IUPAC-IUB Commission on Biochemical Nomenclature, Nomenclature of phosphorus-containing compounds of biochemical importance. Recommendations, 1976. Biochem. J. 171, 1-19 (1978); Eur. J. Biochem. 79, 1-9 (1977); Hoppe-Seyler's Z. Physiol. Chem. 358, 599-616 (1977); Proc. Natl Acad. Sci. USA, 74, 2222-2230 (1977); also pp.203-211 in ref. 4.

8. International Union of Pure and Applied Chemistry (1979) Nomenclature of organic chemistry, Sections A, B, C, D, E, F and H (Rigaudy, J. & Klesney, S. P., eds), Pergamon Press, Oxford.

9. IUPAC-IUB Joint Commission on Biochemical Nomenclature. Nomenclature of tetrapyrroles. Recommendations. 1978. Eur. J. Biochem. 108, 1-30 (1980); Pure Appl. Chem. 51, 2251-2304 (1979).

10. Sections A-1 and A-2.5 of ref. 8, extended by IUPAC Commission on Nomenclature of Organic Chemistry (CNOC). Pure Appl. Chem. 58, 1693-1696 (1986).

11. International Union of Pure and Applied Chemistry (1976) Stereochemistry, Pure Appl. Chem. 45, 11-30 (1976); also pp. 1-5 in ref. 4 and Section E of ref. 8.

12. Takahishi, L., Ogura, K. & Seto, S. (1980) J. Biol. Chem. 255, 4539-4543.

13. Wellburn, A. R. & Hemming, F. W. (1966) Nature (Lond.) 212, 1364-1366.

14. Allen, C. M., Keenan, M. V. & Sack, J. (1976) Arch. Biochem. Biophys. 175, 136-248.

15. Weliburn, A. R., Stevenson, J., Hemming, F. W. & Morton, R. A. ( 1967) Biochem. J. 102, 313-324.

16. Bates. R. B., Gale, D. M. & Gruner. B. J. (1963) J. Org. Chem. 28, 1086-1089.