Homonames

Both skeletal replacement and ‘nor’-type subtractive naming methods can be considered subtypes of skeletal modification nomenclature. And there are more.

Consider homocysteine (a):

(a)	(b)

homocysteine (trivial + ‘homo’ addition) 2-amino-4-sulfanylbutanoic acid (substitutive) cysteine (trivial) 2-amino-3-sulfanylpropanoic acid (substitutive)

The name “homocysteine” is derived from cysteine (b). The prefix ‘homo’ indicates that the structure in question is the next higher member in a homologous series. If cysteine is a “functionalised” propane, then homocysteine is the equally functionalised butane.

It looks like the ‘homo’-type addition is the opposite of ‘nor’-type subtraction, right? Well, not exactly. As we know, ‘nor’ could mean removal of any skeleton atom, including a heteroatom; while ‘homo’ really refers only to insertion of a methylene group, –CH₂–, between two skeletal atoms. If more than one methylene group is added, prefixes ‘dihomo’, ‘trihomo’ etc. are used [1].

(c)	(d)	(e)

unoprostone (trivial) (5Z,9α,11α)-9,11-dihydroxy-15-oxo-20a,20b-dihomoprost-5-en-1-oic acid (substitutive) (5Z,9α,11α)-9,11-dihydroxy-15-oxoprost-5-en-1-oic acid (substitutive) prostanoic acid (trivial, fundamental parent) 7-[(1S,2S)-2-octylcyclopentyl]heptanoic acid (substitutive)

In this naming method, methylene groups inserted into parent structures are not given new locant numbers. Instead, a ‘homo’ carbon atom is given the locant of their immediate neighbour followed by a letter ‘a’, ‘b’, etc. For example, unoprostone (c) can be named as a ‘dihomo’ derivative of (d), which itself is named semisystematically as a derivative of prostanoic acid (e). The use of locants makes names generated this way unambiguous. As the structure (c) can be generated from (d) by insertion of two methylene groups anywhere between positions 15 and 20, nothing prevents me to name the structure (c), say, (5Z,9α,11α)-9,11-dihydroxy-15-oxo-15a,15b-dihomoprost-5-en-1-oic acid (or ‘16a,16b’, ‘17a,17b’, etc.). However, IUPAC recommends to use the highest possible locant for this purpose, so ‘20a,20b’ is the preferred numbering. Likewise, for ‘nor’-type names, it is recommended to remove skeletal atoms with the highest possible locant [2]:

This is done in order to maintain as far as possible traditional numbering of structural features of the compound and of compounds derived from it.

It’s a pity that with ‘homo’ method we cannot insert a heteroatom into a parent structure with the same ease as we can remove one with ‘nor’. Compare the structures (f) and (g):

(f)	(g)

3-aza-4a-homocholest-4a-en-4-one (substitutive + ‘homo’ addition + skeletal replacement) cholest-4-en-3-one (substitutive)

The only difference is the –NH– bridge between carbons 2 and 3 of cholestane skeleton in the structure (f). Ah, why can’t we give it a name saying just that! Alas, for want of a better method, we need two operations instead of one: first, expansion of the A-ring by one carbon atom which we call 4a (because the highest possible locant is 4), therefore ‘4a-homo’; second, skeletal replacement of carbon with nitrogen at the position 3, thus ‘3-aza’. The resulting name is 3-aza-4a-homocholest-4a-en-4-one. The numbering in the expanded ring was affected anyway (I wish it didn’t), but stays intact in the rest of the molecule.

References

1. Giles, Jr., P.M. (1999) Revised Section F: Natural products and related compounds (IUPAC recommendations 1999). Pure and Applied Chemistry 71, 587—643. Rule RF-4.2. Addition of skeletal atoms without affecting the number of rings.
2. Ibid., Rule RF-4.1. Removal of skeletal atoms without affecting the number of rings.